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2. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial

Author

Batagelj, Emilio, Casarini, Ignacio, Pastor, Anea Viviana, Sena, Susana Noemi, Zarba, Juan Jose, Burghuber, Otto, Hartl, Sylvia, Hochmair, Maximilian J, Lamprecht, Bernd, Studnicka, Michael, Alberto Schlittler, Luis, Augusto Martinelli de Oliveira, Fabricio, Calabrich, Aknar, Colagiovanni Girotto, Gustavo, Dos Reis, Peo, Fausto Nino Gorini, Carlos, Rafael Martins De Marchi, Peo, Serodio da Rocha Baldotto, Clarissa, Sette, Claudia, Zukin, Mauro, Conev, Nikolay V, Dudov, Assen, Ilieva, Rumyana, Koynov, Krassimir, Krasteva, Rositsa, Tonev, Ivan, Valev, Spartak, Venkova, Violetka, Bi, Minghong, Chen, Chengshui, Chen, Yuan, Chen, Zhendong, Fang, Jian, Feng, Jifeng, Han, Zhigang, Hu, Jie, Hu, Yi, Li, Wei, Liang, Zongan, Lin, Zhong, Ma, Rui, Ma, Shenglin, Nan, Kejun, Shu, Yongqian, Wang, Kai, Wang, Mengzhao, Wu, Gang, Yang, Nong, Yang, Zhixiong, Zhang, Helong, Zhang, Wei, Zhao, Jun, Zhao, Yanqiu, Zhou, Caicun, Zhou, Jianying, Zhou, Xiangdong, Havel, Libor, Kolek, Vitezslav, Koubkova, Leona, Roubec, Jaromir, Skrickova, Jana, Zemanova, Milada, Chouaid, Christos, Hilgers, Werner, Lena, Hervé, Moro-Sibilot, Denis, Robinet, Gilles, Souquet, Pierre-Jean, Alt, Jürgen, Bischoff, Helge, Grohe, Christian, Laack, Eckart, Lang, Susanne, Panse, Jens, Reinmuth, Niels, Schulz, Christian, Bogos, Krisztina, Csánky, Eszter, Fülöp, Anea, Horváth, Zsolt, Kósa, Judit, Laczó, Ibolya, Losonczy, György, Pajkos, Gábor, Pápai, Zsuzsanna, Pápai Székely, Zsolt, Sárosi, Veronika, Somfay, Attila, Somogyiné Ezer, Éva, Telekes, Anás, Bar, Jair, Gottfried, Maya, Heching, Norman Isaac, Zer Kuch, Alona, Bartolucci, Roberta, Bettini, Anna Cecilia, Delmonte, Angelo, Garassino, Marina Chiara, Minelli, Mauro, Roila, Fausto, Verderame, Francesco, Atagi, Shinji, Azuma, Koichi, Goto, Hisatsugu, Goto, Koichi, Hara, Yu, Hayashi, Hidetoshi, Hida, Toyoaki, Hotta, Katsuyuki, Kanazawa, Kenya, Kanda, Shintaro, Kim, Young Hak, Kuyama, Shoichi, Maeda, Tadashi, Morise, Masahiro, Nakahara, Yasuharu, Nishio, Makoto, Nogami, Naoyuki, Okamoto, Isamu, Saito, Haruhiro, Shinoda, Masahiro, Umemura, Shigeki, Yoshida, Tatsuya, Claessens, Niels, Cornelissen, Robin, Heniks, Lizza, Hiltermann, Jeroen, Smit, Egbert, Staal van den Brekel, Agnes, Kazarnowicz, Andrzej, Kowalski, Dariusz, Mańdziuk, Slawomir, Mróz, Robert, Wojtukiewicz, Marek, Ciuleanu, Tudor, Ganea, Doina, Ungureanu, Anei, Dvorkin, Mikhail, Luft, Alexander, Moiseenko, Vladimir, Poltoratskiy, Artem, Sakaeva, Dina, Smolin, Alexey, Statsenko, Galina, Vasilyev, Alexander, Vladimirova, Lyubov, Anasina, Igor, Chovanec, Jozef, Demo, Pavol, Godal, Robert, Kasan, Peter, Stresko, Marian, Urda, Michal, Cho, Eun Kyung, Ji, Jun Ho, Kim, Joo-Hang, Kim, Sang-We, Lee, Gyeong-Won, Lee, Jong-Seok, Lee, Ki Hyeong, Lee, Kyung Hee, Lee, Yun Gyoo, Amelia Insa Molla, Maria, Domine Gomez, Manuel, Ignacio Delgado Mingorance, Juan, Isla Casado, Dolores, Lopez Brea, Marta, Majem Tarruella, Margarita, Morán Bueno, Teresa, Navarro Mendivil, Alejano, Paz-Ares Rodríguez, Luis, Ponce Aix, Santiago, Rosario Garcia Campelo, Maria, Chang, Gee-Chen, Chen, Yen-Hsun, Chiu, Chao-Hua, Hsia, Te-Chun, Lee, Kang-Yun, Li, Chien-Te, Wang, Chin-Chou, Wei, Yu-Feng, Wu, Shang-Yin, Alacacıoğlu, Ahmet, Çiçin, Irfan, Demirkazik, Ahmet, Erman, Mustafa, Göksel, Tuncay, Özgüroğlu, Mustafa, Adamchuk, Hryhoriy, Bondarenko, Igor, Kolesnik, Oleksii, Kryzhanivska, Anna, Ostapenko, Yuriv, Shevnia, Serhii, Shparyk, Yaroslav, Trukhin, Dmytro, Ursol, Grygorii, Voitko, Nataliia, Voitko, Oleksandr, Vynnychenko, Ihor, Babu, Sunil, Chen, Yuanbin, Chiang, Anne, Chua, Winston, Dakhil, Shaker, Dowlati, Afshin, Goldman, Jonathan W, Haque, Basir, Jamil, Rodney, Knoble, Jeanna, Lakhanpal, Shailena, Mi, Kailhong, Nikolinakos, Petros, Powell, Steven, Ross, Helen, Schaefer, Eric, Schneider, Jeffrey, Spahr, Joseph, Spigel, David, Stilwill, Joseph, Sumey, Christopher, Williamson, Michael, Paz-Ares, Luis, Ponce, Santiago, Armstrong, Jon, Byrne, Natalie, Shire, Norah, and Jiang, Haiyi

Published
2019
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3. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Author

Adamchuk, Grigory, Ahn, Myung-Ju, Alexandru, Aurelia, Altundag, Ozden, Alyasova, Anna, Andrusenko, Orest, Aoe, Keisuke, Araujo, Antonio, Aren, Osvaldo, Arrieta Rodriguez, Oscar, Ativitavas, Touch, Avendano, Oscar, Barata, Fernando, Barrios, Carlos Henrique, Beato, Carlos, Bergstrom, Per, Betticher, Daniel, Bolotina, Larisa, Bondarenko, Igor, Botha, Michiel, Buddu, Sayeuri, Caglevic, Christian, Cardona, Andres, Castro, Gilberto, Jr, Castro, Hugo, Cay Senler, Filiz, Cerny, Carlos Alexandre Sydow, Cesas, Alvydas, Chan, Gee-Chen, Chang, Jianhua, Chen, Gongyan, Chen, Xi, Cheng, Susanna, Cheng, Ying, Cherciu, Nelly, Chiu, Chao-Hua, Cho, Byoung Chul, Cicenas, Saulius, Ciurescu, Daniel, Cohen, Graham, Costa, Marcos Andre, Danchaivijitr, Pongwut, De Angelis, Flavia, de Azevedo, Sergio Jobim, Dediu, Mircea, Deliverski, Tsvetan, De Marchi, Pedro Rafael Martins, de The Bustamante Valles, Flor, Ding, Zhenyu, Doganov, Boyan, Dreosti, Lydia, Duarte, Ricardo, Edusma-Dy, Regina, Emelyanov, Sergey, Erman, Mustafa, Fan, Yun, Fein, Luis, Feng, Jifeng, Fenton, David, Fernandes, Gustavo, Ferreira, Carlos, Franke, Fabio Andre, Freitas, Helano, Fujisaka, Yasuhito, Galindo, Hector, Galvez, Christina, Ganea, Doina, Gil, Nuno, Girotto, Gustavo, Goker, Erdem, Goksel, Tuncay, Gomez Aubin, Gonzalo, Gomez Wolff, Luis, Griph, Hakan, Gumus, Mahmut, Hall, Jacqueline, Hart, Gregory, Havel, Libor, He, Jianxing, He, Yong, Hernandez Hernandez, Carlos, Hespanhol, Venceslau, Hirashima, Tomonori, Ho, Chung Man James, Horiike, Atsushi, Hosomi, Yukio, Hotta, Katsuyuki, Hou, Mei, How, Soon Hin, Hsia, Te-Chun, Hu, Yi, Ichiki, Masao, Imamura, Fumio, Ivashchuk, Oleksandr, Iwamoto, Yasuo, Jaal, Jana, Jassem, Jacek, Jordaan, Christa, Juergens, Rosalyn Anne, Kaen, Diego, Kalinka-Warzocha, Ewa, Karaseva, Nina, Karaszewska, Boguslawa, Kazarnowicz, Andrzej, Kasahara, Kazuo, Katakami, Nobuyuki, Kato, Terufumi, Kawaguchi, Tomoya, Kim, Joo Hang, Kishi, Kazuma, Kolek, Vitezslav, Koleva, Marchela, Kolman, Petr, Koubkova, Leona, Kowalyszyn, Ruben, Kowalski, Dariusz, Koynov, Krassimir, Ksienski, Doran, Kubota, Kaoru, Kudaba, Iveta, Kurata, Takayasu, Kuusk, Gerli, Kuzina, Lyudmila, Laczo, Ibolya, Ladrera, Guia Elena Imelda, Laktionov, Konstantin, Landers, Gregory, Lazarev, Sergey, Lerzo, Guillermo, Lesniewski Kmak, Krzysztof, Li, Wei, Liam, Chong Kin, Lifirenko, Igor, Lipatov, Oleg, Liu, Xiaoqing, Liu, Zhe, Lo, Sing Hung, Lopes, Valeria, Lopez, Karla, Lu, Shun, Martinengo, Gaston, Mas, Luis, Matrosova, Marina, Micheva, Rumyana, Milanova, Zhasmina, Miron, Lucian, Mok, Tony, Molina, Matias, Murakami, Shuji, Nakahara, Yasuharu, Nguyen, Tien Quang, Nishimura, Takashi, Ochsenbein, Adrian, Ohira, Tatsuo, Ohman, Ronny, Ong, Choo Khoon, Ostoros, Gyula, Ouyang, Xuenong, Ovchinnikova, Elena, Ozyilkan, Ozgur, Petruzelka, Lubos, Pham, Xuan Dung, Picon, Pablo, Piko, Bela, Poltoratsky, Artem, Ponomarova, Olga, Popelkova, Patrice, Purkalne, Gunta, Qin, Shukui, Ramlau, Rodryg, Rappaport, Bernardo, Rey, Felipe, Richardet, Eduardo, Roubec, Jaromir, Ruff, Paul, Rusyn, Andrii, Saka, Hideo, Salas, Jorge, Sandoval, Mario, Santos, Lucas, Sawa, Toshiyuki, Seetalarom, Kasan, Seker, Mesut, Seki, Nobuhiko, Seolwane, Freddy, Shepherd, Lucinda, Shevnya, Sergii, Shimada, Andrea Kazumi, Shparyk, Yaroslav, Sinielnikov, Ivan, Sirbu, Daniela, Smaletz, Oren, Soares, Joao Paulo Holanda, Sookprasert, Aumkhae, Speranza, Giovanna, Srimuninnimit, Vichien, Sriuranpong, Virote, Stara, Zinaida, Su, Wu-Chou, Sugawara, Shunichi, Szpak, Waldemar, Takahashi, Kazuhisa, Takigawa, Nagio, Tanaka, Hiroshi, Tan Chun Bing, Jerry, Tang, Qiyou, Taranov, Pavel, Tejada, Hermes, Tho, Lye Mun, Torii, Yoshitaro, Trukhyn, Dmytro, Turdean, Maria, Turna, Hande, Ursol, Grygoriy, Vanasek, Jaroslav, Varela, Mirta, Vallejo, Marcela, Vera, Luis, Victorino, Ana-Paula, Vlasek, Tomas, Vynnychenko, Ihor, Wang, Buhai, Wang, Jie, Wang, Kai, Wu, Yilong, Yamada, Kazuhiko, Yang, Chih-Hsin, Yokoyama, Takuma, Yokoyama, Toshihide, Yoshioka, Hiroshige, Yumuk, Fulden, Zambrano, Angela, Zarba, Juan Jose, Zarubenkov, Oleg, Zemaitis, Marius, Zhang, Li, Zhang, Xin, Zhao, Jun, Zhou, Caicun, Zhou, Jianying, Zhou, Qing, Zippelius, Alfred, Mok, Tony S K, Wu, Yi-Long, Kowalski, Dariusz M, Turna, Hande Z, Laktionov, Konstantin K, Lubiniecki, Gregory M, Zhang, Jin, Kush, Debra, and Lopes, Gilberto

Published
2019
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4. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Harvey, Vernon, Tomek, Rudolf, Robert, Nicholas J., Gore, Ira, Jr., Smith, John W., II, Masuda, Norikazu, Di Sean Kendall, S., Harker, William Graydon, Petrakova, Katarina, Guerrero Zotano, Angel, Simon, Amparo Ruiz, Konstantinovic, Zora Neskovic, Iannotti, Nicholas O., Tassone, Pierfrancesco, Rodriguez, Gladys I., Jáñez Martinez, Noelia, Crespo Massieu, Carmen, Smickoska, Snezana, Somali, Isil, Yilmaz, Ugur, Alonso, Mirta Garcia, Rosales, Adolfo Murias, Cold, Soeren, Knoop, Ann Soegaard, Patt, Debra, Hellerstedt, Beth A., Morales Murillo, Serafin, Mayer, Ingrid A., Means-Powell, Julie Ann, Hui, Rina, Senecal, Francis M., De Boer, Richard Hendry, Shen, Zhenzhou, Luczak, Adam Andrzej, Chui, Joanna W.Y., Tsang, Janice Wing-hang, Lang, Istvan, Rai, Yoshiaki, Hozumi, Yasuo, Ten Tije, Albert J., Bhandari, Manish, Osborne, Cynthia R.C., Ohtani, Shoichiro, Higaki, Kenji, Watanabe, Kenichi, Taguchi, Kazunori, Takahashi, Masato, Filipovic, Sladjana, Hansen, Vincent L., Rao, Vijayarama Phooshkooru, Gupta, Manish, Petrov, Petar, Coudert, Bruno, Vojnovic, Zeljko, Polya, Zsofia, Miyaki, Toshiko, Yamamoto, Naohito, Brincat, Stephen, Lesniewski-Kmak, Krzysztof, Chmielowska, Ewa, Birhiray, Ruemu E., Citron, Marc L., Papish, Steven William, Berry, William R., Langkjer, Sven Tyge, Garcia Sáenz, José Angel, Arance, Ana Maria, Efrat, Noa, Sarosiek, Tomasz, Grzeda, Lukasz, Manalo, Yvonne, Smith, Julie C., Vaziri, Irfan, Healey, Tabitha, Rahim, Yasmin, Luk, Cynthia, Dingle, Brian, Franco, Sandra, Sorensen, Peter Grundtvig, Anand, Anjana, Khan, Sarah, Fountzilas, George, Aogi, Kenjiro, Shimizu, Satoru, Mikulova, Milada, Spanik, Stanislav, Somer, Robert A., Flynn, Patrick J., Coward, Jermaine, Mainwaring, Paul, Jerusalem, Guy, Segura-Ojezzar, Carine, Levy, Christelle, Delozier, Thierry, Khayat, David, Coleman, Robert E., Rolles, Martin J., Maisano, Robert, Nardi, Mario, Ito, Yoshinori, Yumuk, Perran Fulden, Basaran, Gul, Serdar Turhal, Nazim, Wilkinson, Mary J., Green, Nathan B., Sidrys, Algis P., Hallmeyer, Sigrun, Testori, Douglas J., Sridhar, Srikala, Chang, Jose, Sun, Qiang, Jara-Sanchez, Carlos, Rubio, Xabier, Garrido, Maria Lomas, De La Haba Rodriguez, Juan Rafael, Perello Martorell, Antonia, Avelia Mestre, Antoni, Rifa Ferrer, Julio, del Barco Berron, Sonia, Nagy, Zsuzsanna, Tanaka, Maki, Im, Young-Hyuck, Carroll, Robert R., Dickerson, Laura C., Mace, Joseph R., Rivera, Ragene, Klein, Leonard M., Ruxer, Robert, Wilks, Sharon T., Kotasek, Dusan, Popov, Vasil, Taskova, Violina, Marinova-Venkova, Violetka, Timcheva, Constanta, Desbiens, Christine, Ayoub, Jean-Pierre, Grenier, Debjani, Marschner, Norbert, Tesch, Hans, Lueck, Hans-Joachim, Janssen, Jan, Schwaner, Ingo, Wahlstrom, Stine, Brix, Eva Harder, Vallentin, Susanne, Kristensen, Dan, Andreeva, Anna, Glavicic, Vesna, Calvo Plaza, Isabel, Anton Torres, Antonio, Veyret, Corinne, Bergerat, Jean-Pierre, Bourbouloux, Emmanuelle, Ella, Wendy Ann, Algurafi, Hafiz, Robinson, Anne, Kim, Seung Jin, Taguchi, Tetsuya, Juozaityte, Elona, Madretsma, Stanley, Radema, Sandra, Czerniawska-Meier, Malgorzata, Rogowski, Wojciech, Wagnerova, Maria, Richards, Donald A., Tan-Chiu, Elizabeth, Vasileios, Asskikis, Henderson, Charles Arthur, Holden, Viran Roger, Wang, Xiaojia, Tong, Zhongsheng, Yang, Junlan, Gonzalez, Manuel Enrique, Rezai, Mahdi, Hackmann, John, de Dueñas, Eduardo Martinez, de las Heras, Begoña Bermejo, Dourthe, Louis Marie, Chocteau-Bouju, Dorothee, Bougnoux, Philippe, Kakolyris, Stylianos, Kalofonos, Haralabos, Pectasidis, Dimitrios, Ng, Ting Ying, Pajkos, Gabor, Somogyine, Eva Ezer, Tonini, Giuseppe, Giuffrida, Dario, Takao, Shintaro, Ishitobi, Makoto, Inaji, Hideo, Tokuda, Yutaka, Wozniak, Katarzyna, Lungulescu, Dan, Lu, Yen-Shen, Chang, King-Jen, Hill, Julian, Croot, Christopher Charles, Dekker, Albert, Belman, Neil D., Conde, Miguel, Michaelson, Richard A., Kemmer, Kathleen, Chui, Stephen, Luoh, Shiuh-Wen, Nahum, Kenneth, Greenspan, Andrew R., Nichols, Joni C., Encarnacion, Carlos A., Niederman, Thomas M.J., Lee, Theresa, Alexander, Roland, Gordon, Robert, Tomova, Antoanet, Rauch, Daniel, Popescu, Razvan Andrei, Rojas, Gustavo Adolfo, Vanasek, Jaroslav, Neunhoeffer, Tanja, Barinoff, Jana, Graffunder, Gerd, Wolfgang, Abenhardt, Bojko, Peter, Heinrich, Bernhard, von der Assen, Albert, Antonovic, Bogovic Jurij, Adrian, Lene, Ramos Vazquez, Manuel, Gonzalez Santiago, Santiago, Dieras, Veronique, Bishop, Jill Mercia, Perren, Timothy John, Varthalitis, Ioannis, Mavroudis, Dimitris, Georgoulias, Vassilis, Chow, Louis W.C., Yau, Chung Cheung Thomas, Liang, Raymond Hin-Suen, Pikó, Béla, Wéber, Agnes, Kaufman, Bella, Drumea, Karen, Nuzzo, Francesco, De Matteis, Andrea, Carteni, Giacomo, Tokunaga, Eriko, Ishida, Mayumi, Ohno, Shinji, Sato, Nobuaki, Kuroi, Katsumasa, Nishimura, Reiki, Watanabe, Junichiro, Choi, Yoon Ji, Park, Kyong Hwa, Wojtukiewicz, Marek, Jassem, Jacek, Loman, Niklas, Askoy, Sercan, Altundag, Mustafa Kadri, Saip, Pinar, Ali, Muhammad Amjad, Wade, James Lloyd, III, Chien, Amy Jo, Brandt, Debra, Novik, Yelena, Jani, Chirag, Rice, Robert L., Gaffar, Yousuf A. R, Keaton, Mark R., Bajaj, Rajesh, Kimmick, Gretchen, Campbell, David, Turnquest, Theodore, Lucas, Sideras, Dube, Pierre, Xu, Binghe, Schilling, Joerg, Apel, Klaus, Vestlev, Peter Michael, Jensen, Brita Bjerregaard, Haahr, Vera, Lescure, Alvaro Rodriguez, Grana Suarez, Begona, Saura Manich, Cristina, Jacquin, Jean-Philippe, Samreen, Ahmed, Boiangiu, Ion, Dank, Magdolna, Falci, Cristina, Jirillo, Antonio, Cinieri, Saverio, Ueno, Takayuki, Sato, Fumiaki, Yamashiro, Hiroyasu, Sugie, Tomoharu, Lee, Keun Seok, Ro, Jung Sil, Park, In Hae, Bustam, Anita Zarina, Suszko-Kazarnowicz, Malgorzata, Piktel, Artur, Krzemieniecki, Krzysztof, Iorga, Polizenia Georgeta, Yap, Yoon Sim, Kakalejcik, Marian, Sevinc, Alper, Ozguroglu, Mustafa, Chen, Shin-Cheh, Greenberg, Richard H., Eisemann, Allan Daniel, Droder, Robert, Abbasi, M. Rashid, Vaysburd, Marina, Caldera, Humberto Jose, Haley, Barbara Bacsik, Robin, Erwin, Inhorn, Roger C., Hufnagel, David, Kenyon, Peter D., Spremulli, Ellen, Silverman, Paula, Jain, Sharad, Weigand, Robert, Mebis, Jeroen, Koynova, Tatyana, Lesperance, Bernard, Prausova, Jana, Kohne, Claus-Henning, Schneeweiss, Andreas, Jackisch, Christian, Fuxius, Stefan, Cubedo Cervera, Ricardo, Urruticoechea Ribate, Ander, Pernas Simon, Sonia, Valero Gallego, Jose, Arcusa Lanza, Angels, del Pilar Alvarez, Maria, Florian Gerico, Jesus, Cany, Laurent, Stebbing, Justin, Labudovic, Dejan, Gugic, Damir, Vrbanec, Damir, Roila, Fausto, Barni, Sandro, Bidoli, Paolo, Mukai, Hirofumi, Bermudez, Vanessa, Eniu, Alexandru, Mirtsching, Barry C., Ibrahim, Emad, Trey, Joan, Hergenroeder, Paul Francis, Mahmood, Aftab, Gonzalez, Anneliese, Kaplan, Edward H., Ban, Stacy, Patel, Dhimant, Clowney, Billy, Hoelzer, Karen, Schwartz, Garry H., Salkeni, Mohamed, Abraham, Jame, Narula, Sunil, Jabboury, Khaled, Mocharnuk, Robert Scott, McDonough, Richard H., Sikes, David H., Kawanchi, Ronald H., Schlabach, Larry, McCachren, Samuel Spence, Jr., Cosgriff, Thomas M., Dreisbach, Luke, DeMichele, Angela, Pawl, Lawrence, Lucas, Jennifer, Shinn, Lowell C., Alkhouri, Nabiel, Monga, Manish, Lindquist, Deborah L., Anderson, Thomas C., Khurshid, Humera, Witherby, Sabrina, Erickson, Nicholette, Traynor, Ann, Bose, Ron, Pluard, Timothy J., Jones, Michael C., Prakash, Sucharu, Volterra, Fabio, Capo, Gerardo, Flaherty, Lawrence E., Gartner, Elaina, Baidas, Said, Okazaki, Ian, Nguyen, Bichlien, Rakowski, Thomas, Oliff, Ira, Leach, Joseph W., Anderson, Daniel, Kubiak, Kendra, Tsai, Michaela, Vroman, Philippe, Deleu, Ines, Lybaert, Willem, Borms, Marleen, Couture, Felix, Wilson, Jonathan J., Hunt, Gordon, Holland, David R., Mingrone, Walter, Wang, Shusen, Liu, Donggeng, Jiang, Zefei, Benesova, Vera, Smakal, Martin, Garnolova, Petra, Vesper, Anne-Sophie, Neumann, Monika, Janni, Wolfgang, Liedtke, Cornelia, Fischer, Dorothea, Grischke, Eva-Maria, Seeger, Dietmar, Moebus, Volker, Prechtl, Anita, Carlos Camara Toral, Juan, Sanchez Munoz, Alfonso, Gonzalez Jimenez, Sonia, Cassinello Espinosa, Javier, Cirauqui, Beatriz, Margeli Vila, Mireia, Batista Lopez, Norberto, Chacon Lopez-Muniz, Jose Ignacio, de la Cruz Mora, Miguel Angel, Mailliez, Audrey, Vanlemmens, Laurence, Pouessel, Damien, Espie, Marc, Conibear, John, Roylance, Rebecca, Harnett, Adrian, Geffen, David, Ruggeri, Enzo Maria, Gamucci, Teresa, Van Groeningen, Cees J., Banas, Renata, Alkis, Necati, Hou, Ming-Feng, Krie, Amy K., Vrindavanam, Nandagopal S., Howard, Orion M., Citrin, Dennis, Morginstin, Mark S., Desai, Ajit, Sanchez, Ines J., Nixon, David Allen, Jr., Beatty, Patrick G., Edmiston, Kathryn, McLaughlin, Marilyn, Eneman, Jonathan D., Lynch, Cynthia A., O'Brien, Edward, Call, Justin A., Lanier, Keith S., Conlin, Alison, Brooks, Donald J., McIntyre, Kristi, Saltzman, Marc A., Castine, Michael J., III, Ortega, Gregory L., Choi, Young M., Reynolds, Craig H., Brescia, Frankie Ann, Kramer, Rita, Kohn, Aimee D., Micha, John P., Rhee, Jessica M., Shah, Satish, Riseberg, David A., Patterson, William Kevin, Salmon, Jean-Paul, Andre, Chantal, Bols, Alain, D'hondt, Randal, Luce, Sylvie, Nouwynck, Claire, Pelgrims, Gino, Richard, Vincent, Verschuere, Johan, Geldhof, Kurt, Caspar, Clemens, Luo, Rongcheng, Bednarik, Otakar, Schwedler, Kathrin, Schmidt, Marcus, Neumeister, Romy, Bischoff, Joachim, Rack, Brigitte, Repp, Roland, Fries, Stefan, Adrion, Ralf, Schulz, Volker, Klare, Peter, Danei, Mahmoud, Ossenbuhl, Dirk, Kusche, Jakob Manfred, Griesinger, Frank, Baena Canada, Jose Manuel, Martinez del Prado, Purificacion, Machover, David, Mayeur, Didier, Trufflandier, Nathalie, Delecroix, Valerie, Mousseau, Mireille, Mouret-Reynier, Marie-Ange, Nabholtz, Jean-Marc, Chetiyawardana, Anula D., Papandreou, Christos, Hornyak, Lajos, Faluhelyi, Zsolt, Simo, Erzsebet, Di Palma, Mario, Cognetti, Francesco, Gorzegno, Gabriella, Dogliotti, Luigi, Gridelli, Cesare, Falcone, Alfredo, Soto Parra, Hector, Buscarino, Calogero, Im, Seock-Ah, Sanchez Llamas, Benito, Dercksen, Wouter, Erdkamp, Franciscus, Ruit, Jan B., Braun, Hans, Portielje, Joanneke E.A., Ciltas, Aydin, Buyukberber, Suleyman, Benekli, Mustafa, Zahalsky, Andrew J., Jaslow, Rebecca, Thomas, Gary W., Maini, Archana, Wiznitzer, Israel, Khojasteh, Ali, Francisco Gonzalez, Manuel, Kong, Lynn R., Padmanabhan, Aruna, Conkright, William A., Swain, Sandra M., Faig, Douglas E., Jain, Kirti, Yanagihara, Ronald H., Ottaviano, Yvonne, Delmas, Andrew, Steele, Heather A., Rainey, Gordon K., Harris, Penelope J., Burris, Jason K., Rupard, Erik J., Tan, Esther, Whitworth, Pat W., Bova, Abby R., Anderson, Ian C., Shirinian, Mihran, Tin-u, Caesar, O'Rourke, Timothy J., Roberts, Michael S., Francisco, Michael, Pierson, A. Scott, Byeff, Peter D., Kovach, Peter A., Caton, John R., Jr., Rarick, Mark Urban, Schimidt, William G., Jr., Stopeck, Alison T., Swart, Rachel, Carrillo Flores, Maria Regina, Alemany, Carlos A., Lozada, Brennely, Weinstein, Paul L., Wang, Wei, Porubcin, Michael, Ellison, David M., Geils, George F., Rivera, Edgardo, Charif, Mahmoud, Martin, Miguel, Holmes, Frankie A, Ejlertsen, Bent, Delaloge, Suzette, Moy, Beverly, Iwata, Hiroji, von Minckwitz, Gunter, Chia, Stephen K L, Mansi, Janine, Barrios, Carlos H, Gnant, Michael, Tomašević, Zorica, Denduluri, Neelima, Šeparović, Robert, Gokmen, Erhan, Bashford, Anna, Ruiz Borrego, Manuel, Kim, Sung-Bae, Jakobsen, Erik Hugger, Ciceniene, Audrone, Inoue, Kenichi, Overkamp, Friedrich, Heijns, Joan B, Armstrong, Anne C, Link, John S, Joy, Anil Abraham, Bryce, Richard, Wong, Alvin, Moran, Susan, Yao, Bin, Xu, Feng, Auerbach, Alan, Buyse, Marc, and Chan, Arlene

Published
2017
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5. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

Author

Ignatius Ou, SaiHong, Planchard, David, Park, Keunchil, Schuler, Martin, Yang, James, Chand, Vikram, Rohr, Klaus, Bagnes, Claudia, Martin, Claudio Marcelo, Recondo, Gonzalo, Zarba, Juan Jose, Blajman, Cesar, Richardet, Martín, McLachlan, Sue-Anne, Parente, Phillip, Underhill, Craig, Crombie, Catherine, Mainwaring, Paul, Greil, Richard, Humblet, Yves, Bustin, Frédérique, Carestia, Luciano, Galdermans, Danny, Lambrechts, Marc, Delval, Laetitia, Vercauter, Piet, Zhou, Caicun, Wang, Jin, Huang, Cheng, Lin, Xiaoyan, Wu, Yilong, Liu, Xiaoqing, Cheng, Ying, Qin, Shukui, Feng, Jifeng, Huang, Jianjin, Zhang, Yiping, Lu, Shun, Zereu, Manuela, Garicochea, Bernardo, Zadra, Cyntia Albuquerque, Riska, Henrik, Alanko, Tuomo, Cadranel, Jacques, Chouaid, Christos, Zalcman, Gérard, Sibilot, Denis Moro, Perol, Maurice, Bennouna, Jaafar, Fournel, Pierre, Gervais, Radj, Rotarski, Maciej, Coudert, Bruno, Thomas, Michael, Wehler, Thomas, Faehling, Martin, Keilholz, Ulrich, Laack, Eckart, von Pawel, Joachim, Huber, Rudolf, Dickgreber, Nicolas, Wiewrodt, Rainer, Mark, Zsuzsanna, Tehenes, Sandor, Strausz, Janos, Sarosi, Veronika, Prabhash, Kumar, Jain, Minish, Venkatesan, Srinivasan, Sharma, Lalit, Dadhich, Hemant, Nagarkar, Rajnish Vasant, Onn, Amir, Gottfried, Maya, Stemmer, Solomon, Migliorino, Maria Rita, Grossi, Francesco, Bidoli, Paolo, Bearz, Alessandra, Gridelli, Cesare, Milandri, Carlo, Platania, Marco, Ceresoli, Giovanni Luca, Cruciani, Giorgio, Delgado, Francisco Gutierrez, Gonzalez Perez, José Luis, Luna, Gabriela Alvarado, Baca, Othon Padilla, Aerts, J.G.J.V., Stigt, J.A., Dingemans, A.M.C., Herder, G.J.M., Gans, S.J.M., Salas Sánchez, Jorge Fernando, Alvarez Barreda, Renzo Luzgardo, Pantigoso, Wilbert Rodriguez, Palomino, Osbert Luis Mejia, Jaskiewicz, Piotr, Kazarnowicz, Andrzej, Serwatowski, Piotr, Szczesna, Aleksandra, Jassem, Jacek, Lubennikov, Vladimir, Karaseva, Nina, Orlov, Sergey, Ragulin, Yuri, Garrido, Pilar, González Larriba, José Luis, Camps, Carlos, Campelo, Rosario García, Lianes, Pilar, Cobo, Manuel, Felip, Enriqueta, Kim, Dong-Wan, Kim, Sang-We, Kim, Joo-Hang, Han, Ji-Youn, Kim, Young-Chul, Yang, Chih-Hsin, Hsia, Te-Chun, Chen, Yuh-Min, Tsai, Ying-Huang, Chang, Gee-Chen, Tsao, Thomas Chang-Yao, Su, Wu-Chou, Huang, Ming-Shyan, Ho, Ching-Liang, Hsieh, Ruey-Kuen, Vinnyk, Yuriy, Popovych, Oleksandr, Ponomarova, Olga, Bondarenko, Igor, Polishchuk, Iryna, Shah, Riyaz, Mitra, Sanka, Popat, Sanjaykumar, Spicer, James, Toy, Elizabeth, Talbot, Toby, Brown, Emma, Upadhyay, Sunil, Summers, Yvonne, Gurtler, Jayne, Meza, Luis, Thropay, John, Schuler, M., Yang, J.C.-H., Park, K., Kim, J.-H., Bennouna, J., Chen, Y.-M., Chouaid, C., De Marinis, F., Feng, J.-F., Grossi, F., Kim, D.-W., Liu, X., Lu, S., Strausz, J., Vinnyk, Y., Wiewrodt, R., Zhou, C., Wang, B., Chand, V.K., and Planchard, D.

Published
2016
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6. TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial

Author

Quoix, Elisabeth, Lena, Hervé, Losonczy, Gyorgy, Forget, Frédéric, Chouaid, Christos, Papai, Zsolt, Gervais, Radj, Ottensmeier, Christian, Szczesna, Aleksandra, Kazarnowicz, Andrzej, Beck, Joseph T, Westeel, Virginie, Felip, Enriqueta, Debieuvre, Didier, Madroszyk, Anne, Adam, Julien, Lacoste, Gisèle, Tavernaro, Annette, Bastien, Bérangère, Halluard, Céline, Palanché, Tania, and Limacher, Jean-Marc

Published
2016
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7. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial

Author

Thatcher, Nick, Hirsch, Fred R, Luft, Alexander V, Szczesna, Aleksandra, Ciuleanu, Tudor E, Dediu, Mircea, Ramlau, Rodryg, Galiulin, Rinat K, Bálint, Beatrix, Losonczy, György, Kazarnowicz, Andrzej, Park, Keunchil, Schumann, Christian, Reck, Martin, Depenbrock, Henrik, Nanda, Shivani, Kruljac-Letunic, Anamarija, Kurek, Raffael, Paz-Ares, Luis, and Socinski, Mark A

Published
2015
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8. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study

Author

Paz-Ares, Luis, Mezger, Jörg, Ciuleanu, Tudor E, Fischer, Jürgen R, von Pawel, Joachim, Provencio, Mariano, Kazarnowicz, Andrzej, Losonczy, György, de Castro, Gilberto, Jr, Szczesna, Aleksandra, Crino, Lucio, Reck, Martin, Ramlau, Rodryg, Ulsperger, Ernst, Schumann, Christian, Miziara, Jose Elias A, Lessa, Álvaro E, Dediu, Mircea, Bálint, Beatrix, Depenbrock, Henrik, Soldatenkova, Victoria, Kurek, Raffael, Hirsch, Fred R, Thatcher, Nick, and Socinski, Mark A

Published
2015
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10. Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)

Author

Jonathan W Goldman, Mikhail Dvorkin, Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Dmytro Trukhin, Galina Statsenko, Maximilian J Hochmair, Mustafa Özgüroğlu, Jun Ho Ji, Marina Chiara Garassino, Oleksandr Voitko, Artem Poltoratskiy, Santiago Ponce, Francesco Verderame, Libor Havel, Igor Bondarenko, Andrzej Każarnowicz, György Losonczy, Nikolay V Conev, Jon Armstrong, Natalie Byrne, Piruntha Thiyagarajah, Haiyi Jiang, Luis Paz-Ares, Nataliia Voitko, Andrzej Kazarnowicz, Mustafa Özgüroglu, Nikolay Conev, Maximilian Hochmair, Otto Burghuber, Irfan Çiçin, Vladimir Moiseenko, Mustafa Erman, Dariusz Kowalski, Marek Wojtukiewicz, Hryhoriy Adamchuk, Alexander Vasilyev, Serhii Shevnia, Spartak Valev, Maria Amelia Insa Molla, Grygorii Ursol, Anne Chiang, Sylvia Hartl, Zsolt Horváth, Gábor Pajkos, Sang-We Kim, Alexey Smolin, Tuncay Göksel, Shaker Dakhil, Jaromir Roubec, Krisztina Bogos, Robin Cornelissen, Jong-Seok Lee, Maria Rosario Garcia Campelo, Marta Lopez Brea, Ahmet Alacacioglu, Ignacio Casarini, Rumyana Ilieva, Ivan Tonev, Attila Somfay, Jair Bar, Alona Zer Kuch, Mauro Minelli, Roberta Bartolucci, Fausto Roila, Haruhiro Saito, Koichi Azuma, Gyeong-Won Lee, Alexander Luft, Michal Urda, Juan Ignacio Delgado Mingorance, Margarita Majem Tarruella, David Spigel, Krassimir Koynov, Milada Zemanova, Jens Panse, Christian Schulz, Zsolt Pápai Székely, Veronika Sárosi, Angelo Delmonte, Anna Cecilia Bettini, Makoto Nishio, Isamu Okamoto, Lizza Hendriks, Slawomir Mandziuk, Yun Gyoo Lee, Lyubov Vladimirova, Dolores Isla Casado, Manuel Domine Gomez, Alejandro Navarro Mendivil, Teresa Morán Bueno, Shang-Yin Wu, Jeanna Knoble, Jana Skrickova, Violetka Venkova, Werner Hilgers, Eckart Laack, Helge Bischoff, Andrea Fülöp, Ibolya Laczó, Judit Kósa, András Telekes, Tatsuya Yoshida, Shintaro Kanda, Toyoaki Hida, Hidetoshi Hayashi, Tadashi Maeda, Tetsuji Kawamura, Yasuharu Nakahara, Niels Claessens, Ki Hyeong Lee, Chao-Hua Chiu, Sheng-Hao Lin, Chien-Te Li, Ahmet Demirkazik, Eric Schaefer, Petros Nikolinakos, Jeffrey Schneider, Sunil Babu, Bernd Lamprecht, Michael Studnicka, Carlos Fausto Nino Gorini, Juraj Kultan, Vitezslav Kolek, Pierre-Jean Souquet, Denis Moro-Sibilot, Maya Gottfried, Egbert Smit, Kyung Hee Lee, Peter Kasan, Jozef Chovanec, Olexandr Goloborodko, Oleksii Kolesnik, Yuriy Ostapenko, Shailendra Lakhanpal, Basir Haque, Winston Chua, Joseph Stilwill, Susana Noemi Sena, Gustavo Colagiovanni Girotto, Pedro Rafael Martins De Marchi, Fabricio Augusto Martinelli de Oliveira, Pedro Dos Reis, Rositsa Krasteva, Yanqiu Zhao, Chengshui Chen, Leona Koubkova, Gilles Robinet, Christos Chouaid, Christian Grohe, Jürgen Alt, Eszter Csánky, Éva Somogyiné Ezer, Norman Isaac Heching, Young Hak Kim, Shinji Aatagi, Shoichi Kuyama, Daijiro Harada, Naoyuki Nogami, Hiroshi Nokihara, Hisatsugu Goto, Agnes Staal van den Brekel, Eun Kyung Cho, Joo-Hang Kim, Doina Ganea, Tudor Ciuleanu, Ekaterina Popova, Dina Sakaeva, Marian Stresko, Pavol Demo, Robert Godal, Yu-Feng Wei, Yen-Hsun Chen, Te-Chun Hsia, Kang-Yun Lee, Huang-Chih Chang, Chin-Chou Wang, Afshin Dowlati, Christopher Sumey, Steven Powell, Jonathan Goldman, Juan Jose Zarba, Emilio Batagelj, Andrea Viviana Pastor, Mauro Zukin, Clarissa Serodio da Rocha Baldotto, Luis Alberto Schlittler, Aknar Calabrich, Claudia Sette, Asen Dudov, Caicun Zhou, Hervé Lena, Susanne Lang, Zsuzsanna Pápai, Koichi Goto, Shigeki Umemura, Kenya Kanazawa, Yu Hara, Masahiro Shinoda, Masahiro Morise, Jeroen Hiltermann, Robert Mróz, Andrei Ungureanu, Igor Andrasina, Gee-Chen Chang, Ihor Vynnychenko, Yaroslav Shparyk, Anna Kryzhanivska, Helen Ross, Kailhong Mi, Rodney Jamil, Michael Williamson, Joseph Spahr, Zhigang Han, Mengzhao Wang, Zhixiong Yang, Jie Hu, Wei Li, Jun Zhao, Jifeng Feng, Shenglin Ma, Xiangdong Zhou, Zongan Liang, Yi Hu, Yuan Chen, Minghong Bi, Yongqian Shu, Kejun Nan, Jianying Zhou, Wei Zhang, Rui Ma, Nong Yang, Zhong Lin, Gang Wu, Jian Fang, Helong Zhang, Kai Wang, Zhendong Chen, Pulmonary Medicine, and Department of Technology and Operations Management

Subjects
Male, medicine.medical_specialty, Durvalumab, Lung Neoplasms, Time Factors, endocrine system diseases, Population, Antibodies, Monoclonal, Humanized, Gastroenterology, Sudden death, Carboplatin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Progression-free survival, education, Aged, Etoposide, Neoplasm Staging, education.field_of_study, Performance status, business.industry, Antibodies, Monoclonal, Middle Aged, medicine.disease, Small Cell Lung Carcinoma, Progression-Free Survival, Oncology, chemistry, 030220 oncology & carcinogenesis, Disease Progression, Female, Cisplatin, business, Tremelimumab, Febrile neutropenia, medicine.drug
Abstract

Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.

Published
2021
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11. Abstract PD1-04: Results of a phase II double-blinded, randomized, placebo-controlled clinical trial of Indoximod, an Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, in combination with Taxane chemotherapy in metastatic breast cancer (MBC)

Author

Susan A. Melin, Petros Nikolinakos, Shou-Ching Tang, Krzysztof Lesniewski-Kmak, Ibrahim Nuhad, Paul B. Gilman, Veronica Mariotti, Patrick M. Dillon, Oana Cristina Danciu, Dhimant Patel, Eugene P. Kennedy, Alberto J. Montero, Malgorzata Suszko-Kazarnowicz, Hatem Soliman, Andrew Poklepovic, Roohi Ismail-Khan, Hyo S. Han, Boguslawa Karaszewska, Fabio Volterra, Daniel Bruetman, and Timothy Panella

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Taxane, business.industry, Phases of clinical research, Cancer, medicine.disease, Metastatic breast cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Breast cancer, Docetaxel, Median follow-up, 030220 oncology & carcinogenesis, Internal medicine, medicine, Clinical endpoint, business, medicine.drug
Abstract

Background: IDO1 is a mediator of tumor immune suppression through alteration of tryptophan metabolism. Indoximod (1-methyl-tryptophan) is an IDO1 pathway inhibitor. There is preclinical evidence that indoximod acts synergistically with chemotherapy such as taxanes (Uyttenhove, 2003) in an immune dependent fashion. Previous studies demonstrated the safety and activity of indoximod combined with docetaxel in patients with advanced solid tumors, including breast cancer (Soliman, 2014). A phase 2 clinical trial was designed to study the efficacy of indoximod plus taxanes in metastatic breast cancer (MBC) patients (pts). Method: This is a phase II randomized, 1:1 placebo controlled clinical trial, that enrolled MBC pts in multiple centers in the US and Poland. Eligibility criteria included ER+ or ER- HER2- MBC, ability to receive taxane therapy, PS 0-1, normal organ function and absence of autoimmune disease. Pts were randomized to taxane (either weekly paclitaxel 80mg/m2 3 on 1 off or q3wk docetaxel at 75mg/m2 per treating physician’s discretion) + placebo (TP) or taxane + indoximod 1200mg PO BID (TI) as first line treatment for MBC. Primary endpoint was PFS. The sample size of 154 patients was designed to detect a HR of .64 with one sided α=.1 and β=.2 after 95 events. Archival tumor tissue was stained with IHC for IDO1 expression when available. Aperio digital pathology positive pixel algorithm was used for scoring, with manual verification. Median value was used as cut-off for IDO positivity. Results: 164 pts were randomized and treated (85 TI, 79 TP). Demographics and tumor features are shown in table 1. Treatment discontinuation was due to disease progression (60%), adverse events (10%), other (30%). Objective response rate was 40% in TI and 37% in TP arm (p=.74). The median PFS was 6.0 (95% CI, 4.5, 8.1) months in the TI arm and 8.4 (95% CI, 5.6, 9.8) in the TP arm, HR of 1.14 (0.81, 1.60). The median OS was 21.6 months (CI 95%, 16, 39.1) in the TI arm and 21.2 (CI 95%, 19.1, 32.1) in the TP arm. The median follow up was 17.4 (range 0.1, 39.4) months. Grade ≥3 treatment emergent adverse events were observed in 60% of patients in both arms with neutropenia, fatigue, anemia, diarrhea being most common but not significantly different between arms. An exploratory analysis of IDO staining with outcomes in 42 samples (22 in TI and 20 TP) suggested a difference in median PFS in pts with high IDO expression assigned to TI vs. TP (10.3 vs 4 months, p=.047). No other prognostic or predictive associations were observed based on IDO status in the analysis. Conclusions: The combination of indoximod with a taxane in 1st line HER2- MBC was safe and did not result in added toxicity. In an unselected population, no improvement in clinical outcomes was observed for the combination over taxane alone. However, higher tumor IDO expression may select for MBC pts who benefit more from indoximod and should be investigated as a predictive biomarker in future studies. Demographics and tumor featuresIndoximodPlaceboOverallParameterStatistic(N=85)(N=79)(N=164)Age (years)n8579164median (min, max)58 (29,76)57 (29,85)58 (29,85)GenderMalen (%)1 (1.2)2 (2.5)3 (1.8)Femalen (%)84 (98.8)77 (97.5)161 (98.2)RaceWhiten (%)71 (83.5)66 (83.5)137 (83.5)African Americann (%)12 (14.1)10 (12.7)22 (13.4)Asiann (%)1 (1.2)01 (0.6)Othern (%)1 (1.2)3 (3.8)4 (2.4)ECOG status0n (%)41 (48.8)43 (54.4)84 (51.5)1n (%)44 (52.2)36 (44.3)80 (46.6)Hormone Receptor StatusNegativen (%)23 (27.1)23 (29.1)46 (28.0)Positiven (%)62 (72.9)56 (70.9)118 (72.0)Choice of TaxaneDocetaxeln (%)62 (72.9)59 (74.7)121 (73.8)Paclitaxeln (%)23 (27.1)20 (25.3)43 (26.2) Citation Format: Veronica Mariotti, Shou-Ching Tang, Patrick Dillon, Alberto Montero, Andrew Poklepovic, Susan Melin, Ibrahim Nuhad, Petros Nikolinakos, Eugene Kennedy, Hyo Han, Roohi Ismail-Khan, Daniel Bruetman, Oana Danciu, Paul Gilman, Boguslawa Karaszewska, Krzysztof Lesniewski-Kmak, Timothy Panella, Dhimant Patel, Malgorzata Suszko-Kazarnowicz, Fabio Volterra, Hatem Soliman. Results of a phase II double-blinded, randomized, placebo-controlled clinical trial of Indoximod, an Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, in combination with Taxane chemotherapy in metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD1-04.

Published
2020
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12. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

Author

Schuler, M., Yang, J. C.-H., Park, K., Kim, J.-H., Bennouna, J., Chen, Y.-M., Chouaid, C., De Marinis, F., Feng, J.-F., Grossi, F., Kim, D.-W., Liu, X., Lu, S., Strausz, J., Vinnyk, Y., Wiewrodt, R., Zhou, C., Wang, B., Chand, V. K., Planchard, D., Ignatius Ou, Sai Hong, Planchard, David, Park, Keunchil, Schuler, Martin, Yang, James, Chand, Vikram, Rohr, Klaus, Bagnes, Claudia, Martin, Claudio Marcelo, Recondo, Gonzalo, Zarba, Juan Jose, Blajman, Cesar, Richardet, Martín, McLachlan, Sue-Anne, Parente, Phillip, Underhill, Craig, Crombie, Catherine, Mainwaring, Paul, Greil, Richard, Humblet, Yves, Bustin, Frédérique, Carestia, Luciano, Galdermans, Danny, Lambrechts, Marc, Delval, Laetitia, Vercauter, Piet, Zhou, Caicun, Wang, Jin, Huang, Cheng, Lin, Xiaoyan, Wu, Yilong, Liu, Xiaoqing, Cheng, Ying, Qin, Shukui, Feng, Jifeng, Huang, Jianjin, Zhang, Yiping, Lu, Shun, Zereu, Manuela, Garicochea, Bernardo, Zadra, Cyntia Albuquerque, Riska, Henrik, Alanko, Tuomo, Cadranel, Jacques, Chouaid, Christos, Zalcman, Gérard, Sibilot, Denis Moro, Perol, Maurice, Planchard, David, Bennouna, Jaafar, Fournel, Pierre, Gervais, Radj, Rotarski, Maciej, Coudert, Bruno, Schuler, Martin, Thomas, Michael, Wehler, Thomas, Faehling, Martin, Keilholz, Ulrich, Laack, Eckart, von Pawel, Joachim, Huber, Rudolf, Dickgreber, Nicolas, Wiewrodt, Rainer, Mark, Zsuzsanna, Tehenes, Sandor, Strausz, Janos, Sarosi, Veronika, Prabhash, Kumar, Jain, Minish, Venkatesan, Srinivasan, Sharma, Lalit, Dadhich, Hemant, Nagarkar, Rajnish Vasant, Onn, Amir, Gottfried, Maya, Stemmer, Solomon, Migliorino, Maria Rita, Grossi, Francesco, Bidoli, Paolo, Bearz, Alessandra, Gridelli, Cesare, Milandri, Carlo, Platania, Marco, Ceresoli, Giovanni Luca, Cruciani, Giorgio, Delgado, Francisco Gutierrez, Gonzalez Perez, José Luis, Luna, Gabriela Alvarado, Baca, Othon Padilla, Aerts, J.G.J.V., Stigt, J.A., Dingemans, A.M.C., Herder, G.J.M., Gans, S. J. M., Salas Sánchez, Jorge Fernando, Alvarez Barreda, Renzo Luzgardo, Pantigoso, Wilbert Rodriguez, Palomino, Osbert Luis Mejia, Jaskiewicz, Piotr, Kazarnowicz, Andrzej, Serwatowski, Piotr, Szczesna, Aleksandra, Jassem, Jacek, Lubennikov, Vladimir, Karaseva, Nina, Orlov, Sergey, Ragulin, Yuri, Garrido, Pilar, González Larriba, José Luis, Camps, Carlos, Campelo, Rosario García, Lianes, Pilar, Cobo, Manuel, Felip, Enriqueta, Kim, Dong-Wan, Kim, Sang-We, Park, Keunchil, Kim, Joo-Hang, Han, Ji-Youn, Kim, Young-Chul, Yang, Chih-Hsin, Hsia, Te-Chun, Chen, Yuh-Min, Tsai, Ying-Huang, Chang, Gee-Chen, Tsao, Thomas Chang-Yao, Su, Wu-Chou, Huang, Ming-Shyan, Ho, Ching-Liang, Hsieh, Ruey-Kuen, Vinnyk, Yuriy, Popovych, Oleksandr, Ponomarova, Olga, Bondarenko, Igor, Polishchuk, Iryna, Shah, Riyaz, Mitra, Sanka, Popat, Sanjaykumar, Spicer, James, Toy, Elizabeth, Popat, Sanjaykumar, Talbot, Toby, Brown, Emma, Upadhyay, Sunil, Summers, Yvonne, Gurtler, Jayne, Meza, Luis, and Thropay, John

Published
2016
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13. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)

Author

Luis Paz-Ares, Mikhail Dvorkin, Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Dmytro Trukhin, Galina Statsenko, Maximilian J Hochmair, Mustafa Özgüroğlu, Jun Ho Ji, Oleksandr Voitko, Artem Poltoratskiy, Santiago Ponce, Francesco Verderame, Libor Havel, Igor Bondarenko, Andrzej Kazarnowicz, György Losonczy, Nikolay V Conev, Jon Armstrong, Natalie Byrne, Norah Shire, Haiyi Jiang, Jonathan W Goldman, Emilio Batagelj, Ignacio Casarini, Anea Viviana Pastor, Susana Noemi Sena, Juan Jose Zarba, Otto Burghuber, Sylvia Hartl, Bernd Lamprecht, Michael Studnicka, Luis Alberto Schlittler, Fabricio Augusto Martinelli de Oliveira, Aknar Calabrich, Gustavo Colagiovanni Girotto, Peo Dos Reis, Carlos Fausto Nino Gorini, Peo Rafael Martins De Marchi, Clarissa Serodio da Rocha Baldotto, Claudia Sette, Mauro Zukin, Assen Dudov, Rumyana Ilieva, Krassimir Koynov, Rositsa Krasteva, Ivan Tonev, Spartak Valev, Violetka Venkova, Minghong Bi, Chengshui Chen, Yuan Chen, Zhendong Chen, Jian Fang, Jifeng Feng, Zhigang Han, Jie Hu, Yi Hu, Wei Li, Zongan Liang, Zhong Lin, Rui Ma, Shenglin Ma, Kejun Nan, Yongqian Shu, Kai Wang, Mengzhao Wang, Gang Wu, Nong Yang, Zhixiong Yang, Helong Zhang, Wei Zhang, Jun Zhao, Yanqiu Zhao, Caicun Zhou, Jianying Zhou, Xiangdong Zhou, Vitezslav Kolek, Leona Koubkova, Jaromir Roubec, Jana Skrickova, Milada Zemanova, Christos Chouaid, Werner Hilgers, Hervé Lena, Denis Moro-Sibilot, Gilles Robinet, Pierre-Jean Souquet, Jürgen Alt, Helge Bischoff, Christian Grohe, Eckart Laack, Susanne Lang, Jens Panse, Christian Schulz, Krisztina Bogos, Eszter Csánky, Anea Fülöp, Zsolt Horváth, Judit Kósa, Ibolya Laczó, Gábor Pajkos, Zsuzsanna Pápai, Zsolt Pápai Székely, Veronika Sárosi, Attila Somfay, Éva Somogyiné Ezer, Anás Telekes, Jair Bar, Maya Gottfried, Norman Isaac Heching, Alona Zer Kuch, Roberta Bartolucci, Anna Cecilia Bettini, Angelo Delmonte, Marina Chiara Garassino, Mauro Minelli, Fausto Roila, Shinji Atagi, Koichi Azuma, Hisatsugu Goto, Koichi Goto, Yu Hara, Hidetoshi Hayashi, Toyoaki Hida, Kenya Kanazawa, Shintaro Kanda, Young Hak Kim, Shoichi Kuyama, Tadashi Maeda, Masahiro Morise, Yasuharu Nakahara, Makoto Nishio, Naoyuki Nogami, Isamu Okamoto, Haruhiro Saito, Masahiro Shinoda, Shigeki Umemura, Tatsuya Yoshida, Niels Claessens, Robin Cornelissen, Lizza Heniks, Jeroen Hiltermann, Egbert Smit, Agnes Staal van den Brekel, Dariusz Kowalski, Slawomir Mańdziuk, Robert Mróz, Marek Wojtukiewicz, Tudor Ciuleanu, Doina Ganea, Anei Ungureanu, Alexander Luft, Vladimir Moiseenko, Dina Sakaeva, Alexey Smolin, Alexander Vasilyev, Lyubov Vladimirova, Igor Anasina, Jozef Chovanec, Pavol Demo, Robert Godal, Peter Kasan, Marian Stresko, Michal Urda, Eun Kyung Cho, Joo-Hang Kim, Sang-We Kim, Gyeong-Won Lee, Jong-Seok Lee, Ki Hyeong Lee, Kyung Hee Lee, Yun Gyoo Lee, Maria Amelia Insa Molla, Manuel Domine Gomez, Juan Ignacio Delgado Mingorance, Dolores Isla Casado, Marta Lopez Brea, Margarita Majem Tarruella, Teresa Morán Bueno, Alejano Navarro Mendivil, Luis Paz-Ares Rodríguez, Santiago Ponce Aix, Maria Rosario Garcia Campelo, Gee-Chen Chang, Yen-Hsun Chen, Chao-Hua Chiu, Te-Chun Hsia, Kang-Yun Lee, Chien-Te Li, Chin-Chou Wang, Yu-Feng Wei, Shang-Yin Wu, Ahmet Alacacıoğlu, Irfan Çiçin, Ahmet Demirkazik, Mustafa Erman, Tuncay Göksel, Hryhoriy Adamchuk, Oleksii Kolesnik, Anna Kryzhanivska, Yuriv Ostapenko, Serhii Shevnia, Yaroslav Shparyk, Grygorii Ursol, Nataliia Voitko, Ihor Vynnychenko, Sunil Babu, Anne Chiang, Winston Chua, Shaker Dakhil, Afshin Dowlati, Basir Haque, Rodney Jamil, Jeanna Knoble, Shailena Lakhanpal, Kailhong Mi, Petros Nikolinakos, Steven Powell, Helen Ross, Eric Schaefer, Jeffrey Schneider, Joseph Spahr, David Spigel, Joseph Stilwill, Christopher Sumey, and Michael Williamson

Subjects
Male, medicine.medical_specialty, Lung Neoplasms, Durvalumab, Population, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Gastroenterology, Drug Administration Schedule, Carboplatin, 03 medical and health sciences, chemistry.chemical_compound, Antineoplastic Agents, Immunological, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, 030212 general & internal medicine, Progression-free survival, education, Etoposide, Aged, education.field_of_study, Performance status, business.industry, Antibodies, Monoclonal, General Medicine, Middle Aged, Interim analysis, Antineoplastic Agents, Phytogenic, Small Cell Lung Carcinoma, Progression-Free Survival, chemistry, Female, Cisplatin, Prophylactic cranial irradiation, business, medicine.drug
Abstract

Background: Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum–etoposide) in treatment-naive patients with ES-SCLC. Methods: This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum–etoposide; durvalumab plus tremelimumab plus platinum–etoposide; or platinum–etoposide alone. All drugs were administered intravenously. Platinum–etoposide consisted of etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL per min or cisplatin 75–80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum–etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum–etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum–etoposide group versus the platinum–etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. Findings: Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum–etoposide group and 269 to the platinum–etoposide group. Durvalumab plus platinum–etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59–0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5–14·8) in the durvalumab plus platinum–etoposide group versus 10·3 months (9·3–11·2) in the platinum–etoposide group, with 34% (26·9–41·0) versus 25% (18·4–31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum–etoposide group and 166 (62%) of 266 in the platinum–etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. Interpretation: First-line durvalumab plus platinum–etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. Funding: AstraZeneca.

Published
2019

14. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Author

Tony S K Mok, Yi-Long Wu, Iveta Kudaba, Dariusz M Kowalski, Byoung Chul Cho, Hande Z Turna, Gilberto Castro, Vichien Srimuninnimit, Konstantin K Laktionov, Igor Bondarenko, Kaoru Kubota, Gregory M Lubiniecki, Jin Zhang, Debra Kush, Gilberto Lopes, Grigory Adamchuk, Myung-Ju Ahn, Aurelia Alexandru, Ozden Altundag, Anna Alyasova, Orest Andrusenko, Keisuke Aoe, Antonio Araujo, Osvaldo Aren, Oscar Arrieta Rodriguez, Touch Ativitavas, Oscar Avendano, Fernando Barata, Carlos Henrique Barrios, Carlos Beato, Per Bergstrom, Daniel Betticher, Larisa Bolotina, Michiel Botha, Sayeuri Buddu, Christian Caglevic, Andres Cardona, Hugo Castro, Filiz Cay Senler, Carlos Alexandre Sydow Cerny, Alvydas Cesas, Gee-Chen Chan, Jianhua Chang, Gongyan Chen, Xi Chen, Susanna Cheng, Ying Cheng, Nelly Cherciu, Chao-Hua Chiu, Saulius Cicenas, Daniel Ciurescu, Graham Cohen, Marcos Andre Costa, Pongwut Danchaivijitr, Flavia De Angelis, Sergio Jobim de Azevedo, Mircea Dediu, Tsvetan Deliverski, Pedro Rafael Martins De Marchi, Flor de The Bustamante Valles, Zhenyu Ding, Boyan Doganov, Lydia Dreosti, Ricardo Duarte, Regina Edusma-Dy, Sergey Emelyanov, Mustafa Erman, Yun Fan, Luis Fein, Jifeng Feng, David Fenton, Gustavo Fernandes, Carlos Ferreira, Fabio Andre Franke, Helano Freitas, Yasuhito Fujisaka, Hector Galindo, Christina Galvez, Doina Ganea, Nuno Gil, Gustavo Girotto, Erdem Goker, Tuncay Goksel, Gonzalo Gomez Aubin, Luis Gomez Wolff, Hakan Griph, Mahmut Gumus, Jacqueline Hall, Gregory Hart, Libor Havel, Jianxing He, Yong He, Carlos Hernandez Hernandez, Venceslau Hespanhol, Tomonori Hirashima, Chung Man James Ho, Atsushi Horiike, Yukio Hosomi, Katsuyuki Hotta, Mei Hou, Soon Hin How, Te-Chun Hsia, Yi Hu, Masao Ichiki, Fumio Imamura, Oleksandr Ivashchuk, Yasuo Iwamoto, Jana Jaal, Jacek Jassem, Christa Jordaan, Rosalyn Anne Juergens, Diego Kaen, Ewa Kalinka-Warzocha, Nina Karaseva, Boguslawa Karaszewska, Andrzej Kazarnowicz, Kazuo Kasahara, Nobuyuki Katakami, Terufumi Kato, Tomoya Kawaguchi, Joo Hang Kim, Kazuma Kishi, Vitezslav Kolek, Marchela Koleva, Petr Kolman, Leona Koubkova, Ruben Kowalyszyn, Dariusz Kowalski, Krassimir Koynov, Doran Ksienski, Takayasu Kurata, Gerli Kuusk, Lyudmila Kuzina, Ibolya Laczo, Guia Elena Imelda Ladrera, Konstantin Laktionov, Gregory Landers, Sergey Lazarev, Guillermo Lerzo, Krzysztof Lesniewski Kmak, Wei Li, Chong Kin Liam, Igor Lifirenko, Oleg Lipatov, Xiaoqing Liu, Zhe Liu, Sing Hung Lo, Valeria Lopes, Karla Lopez, Shun Lu, Gaston Martinengo, Luis Mas, Marina Matrosova, Rumyana Micheva, Zhasmina Milanova, Lucian Miron, Tony Mok, Matias Molina, Shuji Murakami, Yasuharu Nakahara, Tien Quang Nguyen, Takashi Nishimura, Adrian Ochsenbein, Tatsuo Ohira, Ronny Ohman, Choo Khoon Ong, Gyula Ostoros, Xuenong Ouyang, Elena Ovchinnikova, Ozgur Ozyilkan, Lubos Petruzelka, Xuan Dung Pham, Pablo Picon, Bela Piko, Artem Poltoratsky, Olga Ponomarova, Patrice Popelkova, Gunta Purkalne, Shukui Qin, Rodryg Ramlau, Bernardo Rappaport, Felipe Rey, Eduardo Richardet, Jaromir Roubec, Paul Ruff, Andrii Rusyn, Hideo Saka, Jorge Salas, Mario Sandoval, Lucas Santos, Toshiyuki Sawa, Kasan Seetalarom, Mesut Seker, Nobuhiko Seki, Freddy Seolwane, Lucinda Shepherd, Sergii Shevnya, Andrea Kazumi Shimada, Yaroslav Shparyk, Ivan Sinielnikov, Daniela Sirbu, Oren Smaletz, Joao Paulo Holanda Soares, Aumkhae Sookprasert, Giovanna Speranza, Virote Sriuranpong, Zinaida Stara, Wu-Chou Su, Shunichi Sugawara, Waldemar Szpak, Kazuhisa Takahashi, Nagio Takigawa, Hiroshi Tanaka, Jerry Tan Chun Bing, Qiyou Tang, Pavel Taranov, Hermes Tejada, Lye Mun Tho, Yoshitaro Torii, Dmytro Trukhyn, Maria Turdean, Hande Turna, Grygoriy Ursol, Jaroslav Vanasek, Mirta Varela, Marcela Vallejo, Luis Vera, Ana-Paula Victorino, Tomas Vlasek, Ihor Vynnychenko, Buhai Wang, Jie Wang, Kai Wang, Yilong Wu, Kazuhiko Yamada, Chih-Hsin Yang, Takuma Yokoyama, Toshihide Yokoyama, Hiroshige Yoshioka, Fulden Yumuk, Angela Zambrano, Juan Jose Zarba, Oleg Zarubenkov, Marius Zemaitis, Li Zhang, Xin Zhang, Jun Zhao, Caicun Zhou, Jianying Zhou, Qing Zhou, and Alfred Zippelius

Subjects
medicine.medical_specialty, Chemotherapy, education.field_of_study, Performance status, business.industry, medicine.medical_treatment, Hazard ratio, Population, Phases of clinical research, General Medicine, Pembrolizumab, 030204 cardiovascular system & hematology, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, 030212 general & internal medicine, business, Lung cancer, education
Abstract

Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

Published
2019
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15. Impact of copy number variant and single nucleotide polymorphism of the programmed death-ligand 1 gene, programmed death-ligand 1 protein expression and therapy regimens on overall survival in a large group of Caucasian patients with non-small cell lung carcinoma

Author

Kinga Lew, Paweł Krawczyk, Aleksandra Szczesna, Andrzej Sieracki, Kinga Krukowska, Tomasz Kucharczyk, Bożena Jarosz, Rodryg Ramlau, Robert Kieszko, Andrzej Kazarnowicz, Jan Siwiec, Justyna Błach, Daria Świniuch, Piotr Serwatowski, Tomasz Grodzki, Sebastian Fidler, Iwona Paśnik, Janusz Milanowski, Izabela Chmielewska, Katarzyna Stencel, Aleksandra Bożyk, Michał Gil, Jarosław Buczkowski, Katarzyna Reszka, Tomasz Kubiatowski, Juliusz Pankowski, and Anna Grenda

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, programmed death-ligand 1, medicine.medical_treatment, Single-nucleotide polymorphism, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), single nucleotide polymorphism, Internal medicine, Genotype, Carcinoma, medicine, protein expression, non-small cell lung cancer, Oncogene, business.industry, copy number variation, Cancer, Immunotherapy, Articles, Cell cycle, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, business
Abstract

Anti-programmed death-1 or anti-programmed death-ligand 1 (PD-L1) blockade may be ineffective in some patients with non-small cell lung cancer (NSCLC) with high percentage of tumor cells with PD-L1 expression. In addition, immunotherapy may provide great benefits in patients without PD-L1 expression. The present study assessed PD-L1 protein expression by immunohistochemistry, copy number variation (CNV) of PD-L1 and two single nucleotide polymorphisms (SNPs), rs822335 and rs822336, in the promoter of PD-L1 by quantitative PCR in 673 patients with NSCLC. Overall survival time of patients with NSCLC depending on the assessed predictive factors (PD-L1 CNV or SNP) and the treatment methods (immunotherapy in first/second line of treatment or chemotherapy) was analyzed. The present study revealed significantly higher PD-L1 copies number in patients with ≥10% and ≥50% of tumor cells with PD-L1 expression compared to patients with lower percentage of PD-L1-positive tumor cells (P=0.02 and P=0.0002, respectively). There was a significant positive correlation (R=0.2; P=0.01) between number of PD-L1 copies and percentage of tumor cells with PD-L1 protein expression. Percentage of tumor cells with PD-L1 expression was lower in patients with TT genotype of the rs822335 polymorphism compared to those with CC genotype (P=0.03). The present study observed significantly higher risk of death in patients treated with chemotherapy compared to those treated with immunotherapy (P

Published
2020

16. CASPIAN: OS results from a randomised Phase III study of first-line Durvalumab ± Tremelimumab plus chemotherapy in ED-SCLC: OS-Ergebnisse von CASPIAN, einer randomisierten Phase-III-Studie zur Erstlinientherapie von Durvalumab ± Tremelimumab + Chemotherapie beim Extensive Stage kleinzelligen Lungenkarzinom (ES-SCLC)

Author

A. Poltoratskiy, N. Byrne, Niels Reinmuth, S Ponce, H. Jiang, György Losonczy, A Kazarnowicz, M Özgüroğlu, Jonathan H. Goldman, Maximilian Hochmair, Jon Armstrong, D. Trukhin, J Alt, Norah J. Shire, Oleksandr Voitko, I. Bondarenko, Galina Statsenko, Y. Chen, Nikolay Conev, J Ho Li, Luis Paz-Ares, Libor Havel, Francesco Verderame, and Katsuyuki Hotta

Subjects
Oncology, medicine.medical_specialty, Chemotherapy, Durvalumab, business.industry, Internal medicine, medicine.medical_treatment, First line, Medicine, Extensive stage, business, Tremelimumab, medicine.drug
Published
2020
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17. Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial

Author

Goldman, Jonathan W, primary, Dvorkin, Mikhail, additional, Chen, Yuanbin, additional, Reinmuth, Niels, additional, Hotta, Katsuyuki, additional, Trukhin, Dmytro, additional, Statsenko, Galina, additional, Hochmair, Maximilian J, additional, Özgüroğlu, Mustafa, additional, Ji, Jun Ho, additional, Garassino, Marina Chiara, additional, Voitko, Oleksandr, additional, Poltoratskiy, Artem, additional, Ponce, Santiago, additional, Verderame, Francesco, additional, Havel, Libor, additional, Bondarenko, Igor, additional, Każarnowicz, Andrzej, additional, Losonczy, György, additional, Conev, Nikolay V, additional, Armstrong, Jon, additional, Byrne, Natalie, additional, Thiyagarajah, Piruntha, additional, Jiang, Haiyi, additional, Paz-Ares, Luis, additional, Voitko, Nataliia, additional, Kazarnowicz, Andrzej, additional, Özgüroglu, Mustafa, additional, Conev, Nikolay, additional, Hochmair, Maximilian, additional, Burghuber, Otto, additional, Çiçin, Irfan, additional, Moiseenko, Vladimir, additional, Erman, Mustafa, additional, Kowalski, Dariusz, additional, Wojtukiewicz, Marek, additional, Adamchuk, Hryhoriy, additional, Vasilyev, Alexander, additional, Shevnia, Serhii, additional, Valev, Spartak, additional, Insa Molla, Maria Amelia, additional, Ursol, Grygorii, additional, Chiang, Anne, additional, Hartl, Sylvia, additional, Horváth, Zsolt, additional, Pajkos, Gábor, additional, Kim, Sang-We, additional, Smolin, Alexey, additional, Göksel, Tuncay, additional, Dakhil, Shaker, additional, Roubec, Jaromir, additional, Bogos, Krisztina, additional, Cornelissen, Robin, additional, Lee, Jong-Seok, additional, Garcia Campelo, Maria Rosario, additional, Lopez Brea, Marta, additional, Alacacioglu, Ahmet, additional, Casarini, Ignacio, additional, Ilieva, Rumyana, additional, Tonev, Ivan, additional, Somfay, Attila, additional, Bar, Jair, additional, Zer Kuch, Alona, additional, Minelli, Mauro, additional, Bartolucci, Roberta, additional, Roila, Fausto, additional, Saito, Haruhiro, additional, Azuma, Koichi, additional, Lee, Gyeong-Won, additional, Luft, Alexander, additional, Urda, Michal, additional, Delgado Mingorance, Juan Ignacio, additional, Majem Tarruella, Margarita, additional, Spigel, David, additional, Koynov, Krassimir, additional, Zemanova, Milada, additional, Panse, Jens, additional, Schulz, Christian, additional, Pápai Székely, Zsolt, additional, Sárosi, Veronika, additional, Delmonte, Angelo, additional, Bettini, Anna Cecilia, additional, Nishio, Makoto, additional, Okamoto, Isamu, additional, Hendriks, Lizza, additional, Mandziuk, Slawomir, additional, Lee, Yun Gyoo, additional, Vladimirova, Lyubov, additional, Isla Casado, Dolores, additional, Domine Gomez, Manuel, additional, Navarro Mendivil, Alejandro, additional, Morán Bueno, Teresa, additional, Wu, Shang-Yin, additional, Knoble, Jeanna, additional, Skrickova, Jana, additional, Venkova, Violetka, additional, Hilgers, Werner, additional, Laack, Eckart, additional, Bischoff, Helge, additional, Fülöp, Andrea, additional, Laczó, Ibolya, additional, Kósa, Judit, additional, Telekes, András, additional, Yoshida, Tatsuya, additional, Kanda, Shintaro, additional, Hida, Toyoaki, additional, Hayashi, Hidetoshi, additional, Maeda, Tadashi, additional, Kawamura, Tetsuji, additional, Nakahara, Yasuharu, additional, Claessens, Niels, additional, Lee, Ki Hyeong, additional, Chiu, Chao-Hua, additional, Lin, Sheng-Hao, additional, Li, Chien-Te, additional, Demirkazik, Ahmet, additional, Schaefer, Eric, additional, Nikolinakos, Petros, additional, Schneider, Jeffrey, additional, Babu, Sunil, additional, Lamprecht, Bernd, additional, Studnicka, Michael, additional, Fausto Nino Gorini, Carlos, additional, Kultan, Juraj, additional, Kolek, Vitezslav, additional, Souquet, Pierre-Jean, additional, Moro-Sibilot, Denis, additional, Gottfried, Maya, additional, Smit, Egbert, additional, Lee, Kyung Hee, additional, Kasan, Peter, additional, Chovanec, Jozef, additional, Goloborodko, Olexandr, additional, Kolesnik, Oleksii, additional, Ostapenko, Yuriy, additional, Lakhanpal, Shailendra, additional, Haque, Basir, additional, Chua, Winston, additional, Stilwill, Joseph, additional, Sena, Susana Noemi, additional, Girotto, Gustavo Colagiovanni, additional, De Marchi, Pedro Rafael Martins, additional, Martinelli de Oliveira, Fabricio Augusto, additional, Dos Reis, Pedro, additional, Krasteva, Rositsa, additional, Zhao, Yanqiu, additional, Chen, Chengshui, additional, Koubkova, Leona, additional, Robinet, Gilles, additional, Chouaid, Christos, additional, Grohe, Christian, additional, Alt, Jürgen, additional, Csánky, Eszter, additional, Somogyiné Ezer, Éva, additional, Heching, Norman Isaac, additional, Kim, Young Hak, additional, Aatagi, Shinji, additional, Kuyama, Shoichi, additional, Harada, Daijiro, additional, Nogami, Naoyuki, additional, Nokihara, Hiroshi, additional, Goto, Hisatsugu, additional, Staal van den Brekel, Agnes, additional, Cho, Eun Kyung, additional, Kim, Joo-Hang, additional, Ganea, Doina, additional, Ciuleanu, Tudor, additional, Popova, Ekaterina, additional, Sakaeva, Dina, additional, Stresko, Marian, additional, Demo, Pavol, additional, Godal, Robert, additional, Wei, Yu-Feng, additional, Chen, Yen-Hsun, additional, Hsia, Te-Chun, additional, Lee, Kang-Yun, additional, Chang, Huang-Chih, additional, Wang, Chin-Chou, additional, Dowlati, Afshin, additional, Sumey, Christopher, additional, Powell, Steven, additional, Goldman, Jonathan, additional, Zarba, Juan Jose, additional, Batagelj, Emilio, additional, Pastor, Andrea Viviana, additional, Zukin, Mauro, additional, Baldotto, Clarissa Serodio da Rocha, additional, Schlittler, Luis Alberto, additional, Calabrich, Aknar, additional, Sette, Claudia, additional, Dudov, Asen, additional, Zhou, Caicun, additional, Lena, Hervé, additional, Lang, Susanne, additional, Pápai, Zsuzsanna, additional, Goto, Koichi, additional, Umemura, Shigeki, additional, Kanazawa, Kenya, additional, Hara, Yu, additional, Shinoda, Masahiro, additional, Morise, Masahiro, additional, Hiltermann, Jeroen, additional, Mróz, Robert, additional, Ungureanu, Andrei, additional, Andrasina, Igor, additional, Chang, Gee-Chen, additional, Vynnychenko, Ihor, additional, Shparyk, Yaroslav, additional, Kryzhanivska, Anna, additional, Ross, Helen, additional, Mi, Kailhong, additional, Jamil, Rodney, additional, Williamson, Michael, additional, Spahr, Joseph, additional, Han, Zhigang, additional, Wang, Mengzhao, additional, Yang, Zhixiong, additional, Hu, Jie, additional, Li, Wei, additional, Zhao, Jun, additional, Feng, Jifeng, additional, Ma, Shenglin, additional, Zhou, Xiangdong, additional, Liang, Zongan, additional, Hu, Yi, additional, Chen, Yuan, additional, Bi, Minghong, additional, Shu, Yongqian, additional, Nan, Kejun, additional, Zhou, Jianying, additional, Zhang, Wei, additional, Ma, Rui, additional, Yang, Nong, additional, Lin, Zhong, additional, Wu, Gang, additional, Fang, Jian, additional, Zhang, Helong, additional, Wang, Kai, additional, and Chen, Zhendong, additional

Published
2021
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18. CASPIAN: OS results from a randomised Phase III study of first-line Durvalumab ± Tremelimumab plus chemotherapy in ED-SCLC: OS-Ergebnisse von CASPIAN, einer randomisierten Phase-III-Studie zur Erstlinientherapie von Durvalumab ± Tremelimumab + Chemotherapie beim Extensive Stage kleinzelligen Lungenkarzinom (ES-SCLC)

Author

Reinmuth, N, additional, Paz-Ares, L, additional, Chen, Y, additional, Hotta, K, additional, Trukhin, D, additional, Statsenko, G, additional, Hochmair, MJ, additional, Özgüroğlu, M, additional, Ho Li, J, additional, Voitko, O, additional, Poltoratskiy, A, additional, Ponce, S, additional, Verderame, F, additional, Havel, L, additional, Bondarenko, I, additional, Kazarnowicz, A, additional, Losonczy, G, additional, Conev, NV, additional, Armstrong, J, additional, Byrne, N, additional, Shire, N, additional, Jiang, H, additional, Goldman, J, additional, and Alt, J, additional

Published
2020
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19. Abstract PD1-04: Results of a phase II double-blinded, randomized, placebo-controlled clinical trial of Indoximod, an Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, in combination with Taxane chemotherapy in metastatic breast cancer (MBC)

Author

Mariotti, Veronica, primary, Tang, Shou-Ching, additional, Dillon, Patrick, additional, Montero, Alberto, additional, Poklepovic, Andrew, additional, Melin, Susan, additional, Nuhad, Ibrahim, additional, Nikolinakos, Petros, additional, Kennedy, Eugene, additional, Han, Hyo, additional, Ismail-Khan, Roohi, additional, Bruetman, Daniel, additional, Danciu, Oana, additional, Gilman, Paul, additional, Karaszewska, Boguslawa, additional, Lesniewski-Kmak, Krzysztof, additional, Panella, Timothy, additional, Patel, Dhimant, additional, Suszko-Kazarnowicz, Malgorzata, additional, Volterra, Fabio, additional, and Soliman, Hatem, additional

Published
2020
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20. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial

Author

Nick, Thatcher, Fred R, Hirsch, Alexander V, Luft, Aleksandra, Szczesna, Tudor E, Ciuleanu, Mircea, Dediu, Rodryg, Ramlau, Rinat K, Galiulin, Beatrix, Bálint, György, Losonczy, Andrzej, Kazarnowicz, Keunchil, Park, Christian, Schumann, Martin, Reck, Henrik, Depenbrock, Shivani, Nanda, Anamarija, Kruljac-Letunic, Raffael, Kurek, Luis, Paz-Ares, Mark A, Socinski, Alexander, Spira, Thatcher, N, Hirsch, F, Luft, A, Szczesna, A, Ciuleanu, T, Dediu, M, Ramlau, R, Galiulin, R, Bálint, B, Losonczy, G, Kazarnowicz, A, Park, K, Schumann, C, Reck, M, Depenbrock, H, Nanda, S, Kruljac-Letunic, A, Kurek, R, Paz-Ares, L, Socinski, M, Bidoli, P, Eberhardt, Wilfried (Beitragende*r), and Wilke, Hansjochen (Beitragende*r)

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Lung Neoplasms, Maximum Tolerated Dose, medicine.medical_treatment, Medizin, Phases of clinical research, Kaplan-Meier Estimate, Antibodies, Monoclonal, Humanized, Risk Assessment, Disease-Free Survival, Drug Administration Schedule, Sex Factors, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Invasiveness, Lung cancer, Necitumumab, Aged, Neoplasm Staging, Proportional Hazards Models, Aged, 80 and over, Cisplatin, Chemotherapy, Dose-Response Relationship, Drug, Performance status, Cetuximab, business.industry, Age Factors, Antibodies, Monoclonal, Middle Aged, medicine.disease, Survival Analysis, Gemcitabine, Treatment Outcome, Carcinoma, Squamous Cell, Female, Gentamicins, business, medicine.drug
Abstract

Background: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. Methods: We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m2 administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m2 administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash-a class effect of EGFR antibodies-that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Findings: Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients and randomly assigned them to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11·5 months [95% CI 10·4-12·6]) vs 9·9 months [8·9-11·1]; stratified hazard ratio 0·84 [95% CI 0·74-0·96; p=0·01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group (333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3-4 hypomagnesaemia (47 [9%] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and cisplatin group) and grade 3 rash (20 [4%] vs one [

Published
2015
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23. TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial

Author

Didier Debieuvre, Radj Gervais, Céline Halluard, A. Madroszyk, Enriqueta Felip, Christian H. Ottensmeier, Christos Chouaid, Andrzej Kazarnowicz, Frederic Forget, György Losonczy, Elisabeth Quoix, Annette Tavernaro, Aleksandra Szczesna, Z. Papai, Bérangère Bastien, J.T. Beck, Gisèle Lacoste, Jean Marc Limacher, Julien Adam, Virginie Westeel, Tania Palanché, and Hervé Lena

Subjects
Antigens, Differentiation, T-Lymphocyte, Male, 0301 basic medicine, Lung Neoplasms, Lymphocyte Activation, Deoxycytidine, Carboplatin, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Lymphocytes, Fatigue, education.field_of_study, Membrane Glycoproteins, Hazard ratio, Anemia, Middle Aged, Chemotherapy regimen, CD56 Antigen, Bevacizumab, Oncology, 030220 oncology & carcinogenesis, Predictive value of tests, Female, Immunotherapy, medicine.medical_specialty, Neutropenia, Paclitaxel, Population, Pemetrexed, Placebo, Cancer Vaccines, Disease-Free Survival, Erlotinib Hydrochloride, 03 medical and health sciences, Double-Blind Method, Antigens, CD, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, medicine, Humans, Lectins, C-Type, education, Aged, Performance status, business.industry, Mucin-1, Receptors, IgG, Gemcitabine, Surgery, 030104 developmental biology, Cisplatin, business
Abstract

Summary Background MUC1 is a tumour-associated antigen expressed by many solid tumours, including non-small-cell lung cancer. TG4010 is a modified vaccinia Ankara expressing MUC1 and interleukin 2. In a previous study, TG4010 combined with chemotherapy showed activity in non-small-cell lung cancer and the baseline value of CD16, CD56, CD69 triple-positive activated lymphocytes (TrPAL) was shown to be potentially predictive of TG4010 efficacy. In this phase 2b part of the phase 2b/3 TIME trial, we further assess TG4010 in combination with first-line chemotherapy and use of the TrPAL biomarker in this setting. Methods In this phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial, we recruited previously untreated patients aged 18 years or older with stage IV non-small-cell lung cancer without a known activating EGFR mutation and with MUC1 expression in at least 50% of tumoural cells. Patients were randomly allocated (1:1) by an external service provider to subcutaneous injections of 10 8 plaque-forming units of TG4010 or placebo from the beginning of chemotherapy every week for 6 weeks and then every 3 weeks up to progression, discontinuation for any reason, or toxic effects, stratified according to baseline value of TrPAL (≤ or > the upper limit of normal [ULN]) and, in addition, a dynamic minimisation procedure was used, taking into account chemotherapy regimen, histology, addition or not of bevacizumab, performance status, and centre. Patients, site staff, monitors, the study funder, data managers, and the statistician were masked to treatment identity. The primary endpoint was progression-free survival, assessed every 6 weeks, to validate the predictive value of the TrPAL biomarker. If patients with TrPAL values of less than or equal to the ULN had a Bayesian probability of more than 95% that the true hazard ratio (HR) for progression-free survival was less than 1, and if those with TrPAL values of greater than the ULN had a probability of more than 80% that the true HR for progression-free survival was more than 1, the TrPAL biomarker would be validated. We did primary analyses in the intention-to-treat population and safety analyses in those who had received at least one dose of study drug and had at least one valid post-baseline safety assessment. Monitors, site staff, and patients are still masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT01383148. Findings Between April 10, 2012, and Sept 12, 2014, we randomly allocated 222 patients (TG4010 and chemotherapy 111 [50%]; placebo and chemotherapy 111 [50%]). In the whole population, median progression-free survival was 5·9 months (95% CI 5·4–6·7) in the TG4010 group and 5·1 months (4·2–5·9) in the placebo group (HR 0·74 [95% CI 0·55–0·98]; one-sided p=0·019). In patients with TrPAL values of less than or equal to the ULN, the HR for progression-free survival was 0·75 (0·54–1·03); the posterior probability of the HR being less than 1 was 98·4%, and thus the primary endpoint was met. In patients with TrPAL values of greater than the ULN, the HR for progression-free survival was 0·77 (0·42–1·40); the posterior probability of the HR being greater than 1 was 31·3%, and the primary endpoint was not met. We noted grade 1–2 injection-site reactions in 36 (33%) of 110 patients in the TG4010 group versus four (4%) of 107 patients in the placebo group. We noted no grade 3 or 4 nor serious adverse events deemed to be related to TG4010 only. Four (4%) patients presented grade 3 or 4 adverse events related to TG4010 and other study treatments (chemotherapy or bevacizumab) versus 11 (10%) in the placebo group. No serious adverse event was related to the combination of TG4010 with other study treatments. The most frequent severe adverse events were neutropenia (grade 3 29 [26%], grade 4 13 [12%] in the TG4010 group vs grade 3 22 [21%], grade 4 11 [10%] in the placebo group), anaemia (grade 3 12 [11%] vs grade 3 16 [15%]), and fatigue (grade 3 12 [11%], grade 5 one [1%] vs grade 3 13 [12%]; no grade 4 events). Interpretation TG4010 plus chemotherapy seems to improve progression-free survival relative to placebo plus chemotherapy. These data support the clinical value of the TrPAL biomarker in this clinical setting; because the primary endpoint was met, the trial is to continue into the phase 3 part. Funding Transgene, Avancees Diagnostiques pour de Nouvelles Approches Therapeutiques (ADNA), and OSEO.

Published
2016
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24. PL02.11 Overall Survival with Durvalumab Plus Etoposide-Platinum in First-Line Extensive-Stage SCLC: Results from the CASPIAN Study

Author

Igor Bondarenko, Francesco Verderame, Norah J. Shire, Luis Paz-Ares, Santiago Ponce, Mustafa Ozguroglu, J.H. Ji, A. Poltoratskiy, Libor Havel, Andrzej Kazarnowicz, György Losonczy, Katsuyuki Hotta, Niels Reinmuth, Y. Chen, Nikolay Conev, Maximilian Hochmair, H. Jiang, Jonathan H. Goldman, Jon Armstrong, D. Trukhin, Galina Statsenko, N. Byrne, and Oleksandr Voitko

Subjects
Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Durvalumab, business.industry, First line, chemistry.chemical_element, chemistry, Internal medicine, medicine, Overall survival, Extensive Stage SCLC, business, Platinum, Etoposide, medicine.drug
Published
2019
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25. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial

Author

Paz-Ares, Luis, primary, Dvorkin, Mikhail, additional, Chen, Yuanbin, additional, Reinmuth, Niels, additional, Hotta, Katsuyuki, additional, Trukhin, Dmytro, additional, Statsenko, Galina, additional, Hochmair, Maximilian J, additional, Özgüroğlu, Mustafa, additional, Ji, Jun Ho, additional, Voitko, Oleksandr, additional, Poltoratskiy, Artem, additional, Ponce, Santiago, additional, Verderame, Francesco, additional, Havel, Libor, additional, Bondarenko, Igor, additional, Kazarnowicz, Andrzej, additional, Losonczy, György, additional, Conev, Nikolay V, additional, Armstrong, Jon, additional, Byrne, Natalie, additional, Shire, Norah, additional, Jiang, Haiyi, additional, Goldman, Jonathan W, additional, Batagelj, Emilio, additional, Casarini, Ignacio, additional, Pastor, Anea Viviana, additional, Sena, Susana Noemi, additional, Zarba, Juan Jose, additional, Burghuber, Otto, additional, Hartl, Sylvia, additional, Lamprecht, Bernd, additional, Studnicka, Michael, additional, Alberto Schlittler, Luis, additional, Augusto Martinelli de Oliveira, Fabricio, additional, Calabrich, Aknar, additional, Colagiovanni Girotto, Gustavo, additional, Dos Reis, Peo, additional, Fausto Nino Gorini, Carlos, additional, Rafael Martins De Marchi, Peo, additional, Serodio da Rocha Baldotto, Clarissa, additional, Sette, Claudia, additional, Zukin, Mauro, additional, Dudov, Assen, additional, Ilieva, Rumyana, additional, Koynov, Krassimir, additional, Krasteva, Rositsa, additional, Tonev, Ivan, additional, Valev, Spartak, additional, Venkova, Violetka, additional, Bi, Minghong, additional, Chen, Chengshui, additional, Chen, Yuan, additional, Chen, Zhendong, additional, Fang, Jian, additional, Feng, Jifeng, additional, Han, Zhigang, additional, Hu, Jie, additional, Hu, Yi, additional, Li, Wei, additional, Liang, Zongan, additional, Lin, Zhong, additional, Ma, Rui, additional, Ma, Shenglin, additional, Nan, Kejun, additional, Shu, Yongqian, additional, Wang, Kai, additional, Wang, Mengzhao, additional, Wu, Gang, additional, Yang, Nong, additional, Yang, Zhixiong, additional, Zhang, Helong, additional, Zhang, Wei, additional, Zhao, Jun, additional, Zhao, Yanqiu, additional, Zhou, Caicun, additional, Zhou, Jianying, additional, Zhou, Xiangdong, additional, Kolek, Vitezslav, additional, Koubkova, Leona, additional, Roubec, Jaromir, additional, Skrickova, Jana, additional, Zemanova, Milada, additional, Chouaid, Christos, additional, Hilgers, Werner, additional, Lena, Hervé, additional, Moro-Sibilot, Denis, additional, Robinet, Gilles, additional, Souquet, Pierre-Jean, additional, Alt, Jürgen, additional, Bischoff, Helge, additional, Grohe, Christian, additional, Laack, Eckart, additional, Lang, Susanne, additional, Panse, Jens, additional, Schulz, Christian, additional, Bogos, Krisztina, additional, Csánky, Eszter, additional, Fülöp, Anea, additional, Horváth, Zsolt, additional, Kósa, Judit, additional, Laczó, Ibolya, additional, Pajkos, Gábor, additional, Pápai, Zsuzsanna, additional, Pápai Székely, Zsolt, additional, Sárosi, Veronika, additional, Somfay, Attila, additional, Somogyiné Ezer, Éva, additional, Telekes, Anás, additional, Bar, Jair, additional, Gottfried, Maya, additional, Heching, Norman Isaac, additional, Zer Kuch, Alona, additional, Bartolucci, Roberta, additional, Bettini, Anna Cecilia, additional, Delmonte, Angelo, additional, Garassino, Marina Chiara, additional, Minelli, Mauro, additional, Roila, Fausto, additional, Atagi, Shinji, additional, Azuma, Koichi, additional, Goto, Hisatsugu, additional, Goto, Koichi, additional, Hara, Yu, additional, Hayashi, Hidetoshi, additional, Hida, Toyoaki, additional, Kanazawa, Kenya, additional, Kanda, Shintaro, additional, Kim, Young Hak, additional, Kuyama, Shoichi, additional, Maeda, Tadashi, additional, Morise, Masahiro, additional, Nakahara, Yasuharu, additional, Nishio, Makoto, additional, Nogami, Naoyuki, additional, Okamoto, Isamu, additional, Saito, Haruhiro, additional, Shinoda, Masahiro, additional, Umemura, Shigeki, additional, Yoshida, Tatsuya, additional, Claessens, Niels, additional, Cornelissen, Robin, additional, Heniks, Lizza, additional, Hiltermann, Jeroen, additional, Smit, Egbert, additional, Staal van den Brekel, Agnes, additional, Kowalski, Dariusz, additional, Mańdziuk, Slawomir, additional, Mróz, Robert, additional, Wojtukiewicz, Marek, additional, Ciuleanu, Tudor, additional, Ganea, Doina, additional, Ungureanu, Anei, additional, Luft, Alexander, additional, Moiseenko, Vladimir, additional, Sakaeva, Dina, additional, Smolin, Alexey, additional, Vasilyev, Alexander, additional, Vladimirova, Lyubov, additional, Anasina, Igor, additional, Chovanec, Jozef, additional, Demo, Pavol, additional, Godal, Robert, additional, Kasan, Peter, additional, Stresko, Marian, additional, Urda, Michal, additional, Cho, Eun Kyung, additional, Kim, Joo-Hang, additional, Kim, Sang-We, additional, Lee, Gyeong-Won, additional, Lee, Jong-Seok, additional, Lee, Ki Hyeong, additional, Lee, Kyung Hee, additional, Lee, Yun Gyoo, additional, Amelia Insa Molla, Maria, additional, Domine Gomez, Manuel, additional, Ignacio Delgado Mingorance, Juan, additional, Isla Casado, Dolores, additional, Lopez Brea, Marta, additional, Majem Tarruella, Margarita, additional, Morán Bueno, Teresa, additional, Navarro Mendivil, Alejano, additional, Paz-Ares Rodríguez, Luis, additional, Ponce Aix, Santiago, additional, Rosario Garcia Campelo, Maria, additional, Chang, Gee-Chen, additional, Chen, Yen-Hsun, additional, Chiu, Chao-Hua, additional, Hsia, Te-Chun, additional, Lee, Kang-Yun, additional, Li, Chien-Te, additional, Wang, Chin-Chou, additional, Wei, Yu-Feng, additional, Wu, Shang-Yin, additional, Alacacıoğlu, Ahmet, additional, Çiçin, Irfan, additional, Demirkazik, Ahmet, additional, Erman, Mustafa, additional, Göksel, Tuncay, additional, Adamchuk, Hryhoriy, additional, Kolesnik, Oleksii, additional, Kryzhanivska, Anna, additional, Ostapenko, Yuriv, additional, Shevnia, Serhii, additional, Shparyk, Yaroslav, additional, Ursol, Grygorii, additional, Voitko, Nataliia, additional, Vynnychenko, Ihor, additional, Babu, Sunil, additional, Chiang, Anne, additional, Chua, Winston, additional, Dakhil, Shaker, additional, Dowlati, Afshin, additional, Haque, Basir, additional, Jamil, Rodney, additional, Knoble, Jeanna, additional, Lakhanpal, Shailena, additional, Mi, Kailhong, additional, Nikolinakos, Petros, additional, Powell, Steven, additional, Ross, Helen, additional, Schaefer, Eric, additional, Schneider, Jeffrey, additional, Spahr, Joseph, additional, Spigel, David, additional, Stilwill, Joseph, additional, Sumey, Christopher, additional, and Williamson, Michael, additional

Published
2019
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26. PL02.11 Overall Survival with Durvalumab Plus Etoposide-Platinum in First-Line Extensive-Stage SCLC: Results from the CASPIAN Study

Author

Paz-Ares, L., primary, Chen, Y., additional, Reinmuth, N., additional, Hotta, K., additional, Trukhin, D., additional, Statsenko, G., additional, Hochmair, M.J., additional, Özgüroğlu, M., additional, Ji, J.H., additional, Voitko, O., additional, Poltoratskiy, A., additional, Ponce, S., additional, Verderame, F., additional, Havel, L., additional, Bondarenko, I., additional, Kazarnowicz, A., additional, Losonczy, G., additional, Conev, N.V., additional, Armstrong, J., additional, Byrne, N., additional, Shire, N., additional, Jiang, H., additional, and Goldman, J., additional

Published
2019
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27. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Author

Mok, Tony S K, primary, Wu, Yi-Long, additional, Kudaba, Iveta, additional, Kowalski, Dariusz M, additional, Cho, Byoung Chul, additional, Turna, Hande Z, additional, Castro, Gilberto, additional, Srimuninnimit, Vichien, additional, Laktionov, Konstantin K, additional, Bondarenko, Igor, additional, Kubota, Kaoru, additional, Lubiniecki, Gregory M, additional, Zhang, Jin, additional, Kush, Debra, additional, Lopes, Gilberto, additional, Adamchuk, Grigory, additional, Ahn, Myung-Ju, additional, Alexandru, Aurelia, additional, Altundag, Ozden, additional, Alyasova, Anna, additional, Andrusenko, Orest, additional, Aoe, Keisuke, additional, Araujo, Antonio, additional, Aren, Osvaldo, additional, Arrieta Rodriguez, Oscar, additional, Ativitavas, Touch, additional, Avendano, Oscar, additional, Barata, Fernando, additional, Barrios, Carlos Henrique, additional, Beato, Carlos, additional, Bergstrom, Per, additional, Betticher, Daniel, additional, Bolotina, Larisa, additional, Botha, Michiel, additional, Buddu, Sayeuri, additional, Caglevic, Christian, additional, Cardona, Andres, additional, Castro, Hugo, additional, Cay Senler, Filiz, additional, Cerny, Carlos Alexandre Sydow, additional, Cesas, Alvydas, additional, Chan, Gee-Chen, additional, Chang, Jianhua, additional, Chen, Gongyan, additional, Chen, Xi, additional, Cheng, Susanna, additional, Cheng, Ying, additional, Cherciu, Nelly, additional, Chiu, Chao-Hua, additional, Cicenas, Saulius, additional, Ciurescu, Daniel, additional, Cohen, Graham, additional, Costa, Marcos Andre, additional, Danchaivijitr, Pongwut, additional, De Angelis, Flavia, additional, de Azevedo, Sergio Jobim, additional, Dediu, Mircea, additional, Deliverski, Tsvetan, additional, De Marchi, Pedro Rafael Martins, additional, de The Bustamante Valles, Flor, additional, Ding, Zhenyu, additional, Doganov, Boyan, additional, Dreosti, Lydia, additional, Duarte, Ricardo, additional, Edusma-Dy, Regina, additional, Emelyanov, Sergey, additional, Erman, Mustafa, additional, Fan, Yun, additional, Fein, Luis, additional, Feng, Jifeng, additional, Fenton, David, additional, Fernandes, Gustavo, additional, Ferreira, Carlos, additional, Franke, Fabio Andre, additional, Freitas, Helano, additional, Fujisaka, Yasuhito, additional, Galindo, Hector, additional, Galvez, Christina, additional, Ganea, Doina, additional, Gil, Nuno, additional, Girotto, Gustavo, additional, Goker, Erdem, additional, Goksel, Tuncay, additional, Gomez Aubin, Gonzalo, additional, Gomez Wolff, Luis, additional, Griph, Hakan, additional, Gumus, Mahmut, additional, Hall, Jacqueline, additional, Hart, Gregory, additional, Havel, Libor, additional, He, Jianxing, additional, He, Yong, additional, Hernandez Hernandez, Carlos, additional, Hespanhol, Venceslau, additional, Hirashima, Tomonori, additional, Ho, Chung Man James, additional, Horiike, Atsushi, additional, Hosomi, Yukio, additional, Hotta, Katsuyuki, additional, Hou, Mei, additional, How, Soon Hin, additional, Hsia, Te-Chun, additional, Hu, Yi, additional, Ichiki, Masao, additional, Imamura, Fumio, additional, Ivashchuk, Oleksandr, additional, Iwamoto, Yasuo, additional, Jaal, Jana, additional, Jassem, Jacek, additional, Jordaan, Christa, additional, Juergens, Rosalyn Anne, additional, Kaen, Diego, additional, Kalinka-Warzocha, Ewa, additional, Karaseva, Nina, additional, Karaszewska, Boguslawa, additional, Kazarnowicz, Andrzej, additional, Kasahara, Kazuo, additional, Katakami, Nobuyuki, additional, Kato, Terufumi, additional, Kawaguchi, Tomoya, additional, Kim, Joo Hang, additional, Kishi, Kazuma, additional, Kolek, Vitezslav, additional, Koleva, Marchela, additional, Kolman, Petr, additional, Koubkova, Leona, additional, Kowalyszyn, Ruben, additional, Kowalski, Dariusz, additional, Koynov, Krassimir, additional, Ksienski, Doran, additional, Kurata, Takayasu, additional, Kuusk, Gerli, additional, Kuzina, Lyudmila, additional, Laczo, Ibolya, additional, Ladrera, Guia Elena Imelda, additional, Laktionov, Konstantin, additional, Landers, Gregory, additional, Lazarev, Sergey, additional, Lerzo, Guillermo, additional, Lesniewski Kmak, Krzysztof, additional, Li, Wei, additional, Liam, Chong Kin, additional, Lifirenko, Igor, additional, Lipatov, Oleg, additional, Liu, Xiaoqing, additional, Liu, Zhe, additional, Lo, Sing Hung, additional, Lopes, Valeria, additional, Lopez, Karla, additional, Lu, Shun, additional, Martinengo, Gaston, additional, Mas, Luis, additional, Matrosova, Marina, additional, Micheva, Rumyana, additional, Milanova, Zhasmina, additional, Miron, Lucian, additional, Mok, Tony, additional, Molina, Matias, additional, Murakami, Shuji, additional, Nakahara, Yasuharu, additional, Nguyen, Tien Quang, additional, Nishimura, Takashi, additional, Ochsenbein, Adrian, additional, Ohira, Tatsuo, additional, Ohman, Ronny, additional, Ong, Choo Khoon, additional, Ostoros, Gyula, additional, Ouyang, Xuenong, additional, Ovchinnikova, Elena, additional, Ozyilkan, Ozgur, additional, Petruzelka, Lubos, additional, Pham, Xuan Dung, additional, Picon, Pablo, additional, Piko, Bela, additional, Poltoratsky, Artem, additional, Ponomarova, Olga, additional, Popelkova, Patrice, additional, Purkalne, Gunta, additional, Qin, Shukui, additional, Ramlau, Rodryg, additional, Rappaport, Bernardo, additional, Rey, Felipe, additional, Richardet, Eduardo, additional, Roubec, Jaromir, additional, Ruff, Paul, additional, Rusyn, Andrii, additional, Saka, Hideo, additional, Salas, Jorge, additional, Sandoval, Mario, additional, Santos, Lucas, additional, Sawa, Toshiyuki, additional, Seetalarom, Kasan, additional, Seker, Mesut, additional, Seki, Nobuhiko, additional, Seolwane, Freddy, additional, Shepherd, Lucinda, additional, Shevnya, Sergii, additional, Shimada, Andrea Kazumi, additional, Shparyk, Yaroslav, additional, Sinielnikov, Ivan, additional, Sirbu, Daniela, additional, Smaletz, Oren, additional, Soares, Joao Paulo Holanda, additional, Sookprasert, Aumkhae, additional, Speranza, Giovanna, additional, Sriuranpong, Virote, additional, Stara, Zinaida, additional, Su, Wu-Chou, additional, Sugawara, Shunichi, additional, Szpak, Waldemar, additional, Takahashi, Kazuhisa, additional, Takigawa, Nagio, additional, Tanaka, Hiroshi, additional, Tan Chun Bing, Jerry, additional, Tang, Qiyou, additional, Taranov, Pavel, additional, Tejada, Hermes, additional, Tho, Lye Mun, additional, Torii, Yoshitaro, additional, Trukhyn, Dmytro, additional, Turdean, Maria, additional, Turna, Hande, additional, Ursol, Grygoriy, additional, Vanasek, Jaroslav, additional, Varela, Mirta, additional, Vallejo, Marcela, additional, Vera, Luis, additional, Victorino, Ana-Paula, additional, Vlasek, Tomas, additional, Vynnychenko, Ihor, additional, Wang, Buhai, additional, Wang, Jie, additional, Wang, Kai, additional, Wu, Yilong, additional, Yamada, Kazuhiko, additional, Yang, Chih-Hsin, additional, Yokoyama, Takuma, additional, Yokoyama, Toshihide, additional, Yoshioka, Hiroshige, additional, Yumuk, Fulden, additional, Zambrano, Angela, additional, Zarba, Juan Jose, additional, Zarubenkov, Oleg, additional, Zemaitis, Marius, additional, Zhang, Li, additional, Zhang, Xin, additional, Zhao, Jun, additional, Zhou, Caicun, additional, Zhou, Jianying, additional, Zhou, Qing, additional, and Zippelius, Alfred, additional

Published
2019
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28. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

Author

M. Schuler, J.C.-H. Yang, K. Park, J.-H. Kim, J. Bennouna, Y.-M. Chen, C. Chouaid, F. De Marinis, J.-F. Feng, F. Grossi, D.-W. Kim, X. Liu, S. Lu, J. Strausz, Y. Vinnyk, R. Wiewrodt, C. Zhou, B. Wang, V.K. Chand, D. Planchard, SaiHong Ignatius Ou, David Planchard, Keunchil Park, Martin Schuler, James Yang, Vikram Chand, Klaus Rohr, Claudia Bagnes, Claudio Marcelo Martin, Gonzalo Recondo, Juan Jose Zarba, Cesar Blajman, Martín Richardet, Sue-Anne McLachlan, Phillip Parente, Craig Underhill, Catherine Crombie, Paul Mainwaring, Richard Greil, Yves Humblet, Frédérique Bustin, Luciano Carestia, Danny Galdermans, Marc Lambrechts, Laetitia Delval, Piet Vercauter, Caicun Zhou, Jin Wang, Cheng Huang, Xiaoyan Lin, Yilong Wu, Xiaoqing Liu, Ying Cheng, Shukui Qin, Jifeng Feng, Jianjin Huang, Yiping Zhang, Shun Lu, Manuela Zereu, Bernardo Garicochea, Cyntia Albuquerque Zadra, Henrik Riska, Tuomo Alanko, Jacques Cadranel, Christos Chouaid, Gérard Zalcman, Denis Moro Sibilot, Maurice Perol, Jaafar Bennouna, Pierre Fournel, Radj Gervais, Maciej Rotarski, Bruno Coudert, Michael Thomas, Thomas Wehler, Martin Faehling, Ulrich Keilholz, Eckart Laack, Joachim von Pawel, Rudolf Huber, Nicolas Dickgreber, Rainer Wiewrodt, Zsuzsanna Mark, Sandor Tehenes, Janos Strausz, Veronika Sarosi, Kumar Prabhash, Minish Jain, Srinivasan Venkatesan, Lalit Sharma, Hemant Dadhich, Rajnish Vasant Nagarkar, Amir Onn, Maya Gottfried, Solomon Stemmer, Maria Rita Migliorino, Francesco Grossi, Paolo Bidoli, Alessandra Bearz, Cesare Gridelli, Carlo Milandri, Marco Platania, Giovanni Luca Ceresoli, Giorgio Cruciani, Francisco Gutierrez Delgado, José Luis Gonzalez Perez, Gabriela Alvarado Luna, Othon Padilla Baca, J.G.J.V. Aerts, J.A. Stigt, A.M.C. Dingemans, G.J.M. Herder, S.J.M. Gans, Jorge Fernando Salas Sánchez, Renzo Luzgardo Alvarez Barreda, Wilbert Rodriguez Pantigoso, Osbert Luis Mejia Palomino, Piotr Jaskiewicz, Andrzej Kazarnowicz, Piotr Serwatowski, Aleksandra Szczesna, Jacek Jassem, Vladimir Lubennikov, Nina Karaseva, Sergey Orlov, Yuri Ragulin, Pilar Garrido, José Luis González Larriba, Carlos Camps, Rosario García Campelo, Pilar Lianes, Manuel Cobo, Enriqueta Felip, Dong-Wan Kim, Sang-We Kim, Joo-Hang Kim, Ji-Youn Han, Young-Chul Kim, Chih-Hsin Yang, Te-Chun Hsia, Yuh-Min Chen, Ying-Huang Tsai, Gee-Chen Chang, Thomas Chang-Yao Tsao, Wu-Chou Su, Ming-Shyan Huang, Ching-Liang Ho, Ruey-Kuen Hsieh, Yuriy Vinnyk, Oleksandr Popovych, Olga Ponomarova, Igor Bondarenko, Iryna Polishchuk, Riyaz Shah, Sanka Mitra, Sanjaykumar Popat, James Spicer, Elizabeth Toy, Toby Talbot, Emma Brown, Sunil Upadhyay, Yvonne Summers, Jayne Gurtler, Luis Meza, John Thropay, Schuler, M, Yang, J, Park, K, Kim, J, Bennouna, J, Chen, Y, Chouaid, C, De Marinis, F, Feng, J, Grossi, F, Kim, D, Liu, X, Lu, S, Strausz, J, Vinnyk, Y, Wiewrodt, R, Zhou, C, Wang, B, Chand, V, Planchard, D, and Bidoli, P

Subjects
0301 basic medicine, Oncology, Male, Lung Neoplasms, medicine.medical_treatment, Afatinib, Medizin, NSCLC, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Medicine, heterocyclic compounds, Prospective Studies, skin and connective tissue diseases, Erlotinib Hydrochloride, Hematology, Middle Aged, OPEN-LABEL, Chemotherapy regimen, 030220 oncology & carcinogenesis, SURVIVAL, Disease Progression, Female, Erlotinib, Life Sciences & Biomedicine, CLINICAL-TRIALS, medicine.drug, medicine.medical_specialty, BIBW 2992, Paclitaxel, DISCONTINUATION, ERLOTINIB, Antineoplastic Agents, Disease-Free Survival, GEFITINIB, 03 medical and health sciences, Gefitinib, Internal medicine, TYROSINE KINASE INHIBITORS, Humans, Progression-free survival, Oncology & Carcinogenesis, Lung cancer, neoplasms, Protein Kinase Inhibitors, Chemotherapy, Science & Technology, business.industry, EGFR MUTATIONS, Squamous cell, medicine.disease, respiratory tract diseases, 030104 developmental biology, LUX-Lung 5 Investigators, Quinazolines, Receptor, Epidermal Growth Factor, business, 1112 Oncology And Carcinogenesis, ACQUIRED-RESISTANCE
Abstract

Background: Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. Patients and methods: Patients with relapsed/refractory disease following ≥ 1 line of chemotherapy, and whose tumors had progressed following initial disease control (≥ 12 weeks) with erlotinib/gefitinib and thereafter afatinib (50 mg/day), were randomized 2:1 to receive afatinib plus paclitaxel (40 mg/day; 80 mg/m2/week) or investigator's choice of single-agent chemotherapy. The primary end point was progression-free survival (PFS). Other end points included objective response rate (ORR), overall survival (OS), safety and patient-reported outcomes. Results: Two hundred and two patients with progressive disease following clinical benefit from afatinib were randomized to afatinib plus paclitaxel (n ≥ 134) or single-agent chemotherapy (n ≥ 68). PFS (median 5.6 versus 2.8 months, hazard ratio 0.60, P ≥ 0.003) and ORR (32.1% versus 13.2%, P ≥ 0.005) significantly improved with afatinib plus paclitaxel. There was no difference in OS. Global health status/quality of life was maintained with afatinib plus paclitaxel over the entire treatment period. The median treatment duration was 133 and 51 days with afatinib plus paclitaxel and single-agent chemotherapy, respectively; 48.5% of patients receiving afatinib plus paclitaxel and 30.0% of patients receiving single-agent chemotherapy experienced drug-related grade 3/4 adverse events. Treatment-related adverse events were consistent with those previously reported with each agent. Conclusion: Afatinib plus paclitaxel improved PFS and ORR compared with single-agent chemotherapy in patients who acquired resistance to erlotinib/gefitinib and progressed on afatinib after initial benefit. LUX-Lung 5 is the first prospective trial to demonstrate the benefit of continued ErbB targeting post-progression, versus switching to single-agent chemotherapy. Trial registration number: NCT01085136 (clinicaltrials.gov).

Published
2016

29. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Martin, Miguel, primary, Holmes, Frankie A, additional, Ejlertsen, Bent, additional, Delaloge, Suzette, additional, Moy, Beverly, additional, Iwata, Hiroji, additional, von Minckwitz, Gunter, additional, Chia, Stephen K L, additional, Mansi, Janine, additional, Barrios, Carlos H, additional, Gnant, Michael, additional, Tomašević, Zorica, additional, Denduluri, Neelima, additional, Šeparović, Robert, additional, Gokmen, Erhan, additional, Bashford, Anna, additional, Ruiz Borrego, Manuel, additional, Kim, Sung-Bae, additional, Jakobsen, Erik Hugger, additional, Ciceniene, Audrone, additional, Inoue, Kenichi, additional, Overkamp, Friedrich, additional, Heijns, Joan B, additional, Armstrong, Anne C, additional, Link, John S, additional, Joy, Anil Abraham, additional, Bryce, Richard, additional, Wong, Alvin, additional, Moran, Susan, additional, Yao, Bin, additional, Xu, Feng, additional, Auerbach, Alan, additional, Buyse, Marc, additional, Chan, Arlene, additional, Harvey, Vernon, additional, Tomek, Rudolf, additional, Robert, Nicholas J., additional, Gore, Ira, additional, Smith, John W., additional, Masuda, Norikazu, additional, Di Sean Kendall, S., additional, Harker, William Graydon, additional, Petrakova, Katarina, additional, Guerrero Zotano, Angel, additional, Simon, Amparo Ruiz, additional, Konstantinovic, Zora Neskovic, additional, Iannotti, Nicholas O., additional, Tassone, Pierfrancesco, additional, Rodriguez, Gladys I., additional, Jáñez Martinez, Noelia, additional, Crespo Massieu, Carmen, additional, Smickoska, Snezana, additional, Somali, Isil, additional, Yilmaz, Ugur, additional, Alonso, Mirta Garcia, additional, Rosales, Adolfo Murias, additional, Cold, Soeren, additional, Knoop, Ann Soegaard, additional, Patt, Debra, additional, Hellerstedt, Beth A., additional, Morales Murillo, Serafin, additional, Mayer, Ingrid A., additional, Means-Powell, Julie Ann, additional, Hui, Rina, additional, Senecal, Francis M., additional, De Boer, Richard Hendry, additional, Shen, Zhenzhou, additional, Luczak, Adam Andrzej, additional, Chui, Joanna W.Y., additional, Tsang, Janice Wing-hang, additional, Lang, Istvan, additional, Rai, Yoshiaki, additional, Hozumi, Yasuo, additional, Ten Tije, Albert J., additional, Bhandari, Manish, additional, Osborne, Cynthia R.C., additional, Ohtani, Shoichiro, additional, Higaki, Kenji, additional, Watanabe, Kenichi, additional, Taguchi, Kazunori, additional, Takahashi, Masato, additional, Filipovic, Sladjana, additional, Hansen, Vincent L., additional, Rao, Vijayarama Phooshkooru, additional, Gupta, Manish, additional, Petrov, Petar, additional, Coudert, Bruno, additional, Vojnovic, Zeljko, additional, Polya, Zsofia, additional, Miyaki, Toshiko, additional, Yamamoto, Naohito, additional, Brincat, Stephen, additional, Lesniewski-Kmak, Krzysztof, additional, Chmielowska, Ewa, additional, Birhiray, Ruemu E., additional, Citron, Marc L., additional, Papish, Steven William, additional, Berry, William R., additional, Langkjer, Sven Tyge, additional, Garcia Sáenz, José Angel, additional, Arance, Ana Maria, additional, Efrat, Noa, additional, Sarosiek, Tomasz, additional, Grzeda, Lukasz, additional, Manalo, Yvonne, additional, Smith, Julie C., additional, Vaziri, Irfan, additional, Healey, Tabitha, additional, Rahim, Yasmin, additional, Luk, Cynthia, additional, Dingle, Brian, additional, Franco, Sandra, additional, Sorensen, Peter Grundtvig, additional, Anand, Anjana, additional, Khan, Sarah, additional, Fountzilas, George, additional, Aogi, Kenjiro, additional, Shimizu, Satoru, additional, Mikulova, Milada, additional, Spanik, Stanislav, additional, Somer, Robert A., additional, Flynn, Patrick J., additional, Coward, Jermaine, additional, Mainwaring, Paul, additional, Jerusalem, Guy, additional, Segura-Ojezzar, Carine, additional, Levy, Christelle, additional, Delozier, Thierry, additional, Khayat, David, additional, Coleman, Robert E., additional, Rolles, Martin J., additional, Maisano, Robert, additional, Nardi, Mario, additional, Ito, Yoshinori, additional, Yumuk, Perran Fulden, additional, Basaran, Gul, additional, Serdar Turhal, Nazim, additional, Wilkinson, Mary J., additional, Green, Nathan B., additional, Sidrys, Algis P., additional, Hallmeyer, Sigrun, additional, Testori, Douglas J., additional, Sridhar, Srikala, additional, Chang, Jose, additional, Sun, Qiang, additional, Jara-Sanchez, Carlos, additional, Rubio, Xabier, additional, Garrido, Maria Lomas, additional, De La Haba Rodriguez, Juan Rafael, additional, Perello Martorell, Antonia, additional, Avelia Mestre, Antoni, additional, Rifa Ferrer, Julio, additional, del Barco Berron, Sonia, additional, Nagy, Zsuzsanna, additional, Tanaka, Maki, additional, Im, Young-Hyuck, additional, Carroll, Robert R., additional, Dickerson, Laura C., additional, Mace, Joseph R., additional, Rivera, Ragene, additional, Klein, Leonard M., additional, Ruxer, Robert, additional, Wilks, Sharon T., additional, Kotasek, Dusan, additional, Popov, Vasil, additional, Taskova, Violina, additional, Marinova-Venkova, Violetka, additional, Timcheva, Constanta, additional, Desbiens, Christine, additional, Ayoub, Jean-Pierre, additional, Grenier, Debjani, additional, Marschner, Norbert, additional, Tesch, Hans, additional, Lueck, Hans-Joachim, additional, Janssen, Jan, additional, Schwaner, Ingo, additional, Wahlstrom, Stine, additional, Brix, Eva Harder, additional, Vallentin, Susanne, additional, Kristensen, Dan, additional, Andreeva, Anna, additional, Glavicic, Vesna, additional, Calvo Plaza, Isabel, additional, Anton Torres, Antonio, additional, Veyret, Corinne, additional, Bergerat, Jean-Pierre, additional, Bourbouloux, Emmanuelle, additional, Ella, Wendy Ann, additional, Algurafi, Hafiz, additional, Robinson, Anne, additional, Kim, Seung Jin, additional, Taguchi, Tetsuya, additional, Juozaityte, Elona, additional, Madretsma, Stanley, additional, Radema, Sandra, additional, Czerniawska-Meier, Malgorzata, additional, Rogowski, Wojciech, additional, Wagnerova, Maria, additional, Richards, Donald A., additional, Tan-Chiu, Elizabeth, additional, Vasileios, Asskikis, additional, Henderson, Charles Arthur, additional, Holden, Viran Roger, additional, Wang, Xiaojia, additional, Tong, Zhongsheng, additional, Yang, Junlan, additional, Gonzalez, Manuel Enrique, additional, Rezai, Mahdi, additional, Hackmann, John, additional, de Dueñas, Eduardo Martinez, additional, de las Heras, Begoña Bermejo, additional, Dourthe, Louis Marie, additional, Chocteau-Bouju, Dorothee, additional, Bougnoux, Philippe, additional, Kakolyris, Stylianos, additional, Kalofonos, Haralabos, additional, Pectasidis, Dimitrios, additional, Ng, Ting Ying, additional, Pajkos, Gabor, additional, Somogyine, Eva Ezer, additional, Tonini, Giuseppe, additional, Giuffrida, Dario, additional, Takao, Shintaro, additional, Ishitobi, Makoto, additional, Inaji, Hideo, additional, Tokuda, Yutaka, additional, Wozniak, Katarzyna, additional, Lungulescu, Dan, additional, Lu, Yen-Shen, additional, Chang, King-Jen, additional, Hill, Julian, additional, Croot, Christopher Charles, additional, Dekker, Albert, additional, Belman, Neil D., additional, Conde, Miguel, additional, Michaelson, Richard A., additional, Kemmer, Kathleen, additional, Chui, Stephen, additional, Luoh, Shiuh-Wen, additional, Nahum, Kenneth, additional, Greenspan, Andrew R., additional, Nichols, Joni C., additional, Encarnacion, Carlos A., additional, Niederman, Thomas M.J., additional, Lee, Theresa, additional, Alexander, Roland, additional, Gordon, Robert, additional, Tomova, Antoanet, additional, Rauch, Daniel, additional, Popescu, Razvan Andrei, additional, Rojas, Gustavo Adolfo, additional, Vanasek, Jaroslav, additional, Neunhoeffer, Tanja, additional, Barinoff, Jana, additional, Graffunder, Gerd, additional, Wolfgang, Abenhardt, additional, Bojko, Peter, additional, Heinrich, Bernhard, additional, von der Assen, Albert, additional, Antonovic, Bogovic Jurij, additional, Adrian, Lene, additional, Ramos Vazquez, Manuel, additional, Gonzalez Santiago, Santiago, additional, Dieras, Veronique, additional, Bishop, Jill Mercia, additional, Perren, Timothy John, additional, Varthalitis, Ioannis, additional, Mavroudis, Dimitris, additional, Georgoulias, Vassilis, additional, Chow, Louis W.C., additional, Yau, Chung Cheung Thomas, additional, Liang, Raymond Hin-Suen, additional, Pikó, Béla, additional, Wéber, Agnes, additional, Kaufman, Bella, additional, Drumea, Karen, additional, Nuzzo, Francesco, additional, De Matteis, Andrea, additional, Carteni, Giacomo, additional, Tokunaga, Eriko, additional, Ishida, Mayumi, additional, Ohno, Shinji, additional, Sato, Nobuaki, additional, Kuroi, Katsumasa, additional, Nishimura, Reiki, additional, Watanabe, Junichiro, additional, Choi, Yoon Ji, additional, Park, Kyong Hwa, additional, Wojtukiewicz, Marek, additional, Jassem, Jacek, additional, Loman, Niklas, additional, Askoy, Sercan, additional, Altundag, Mustafa Kadri, additional, Saip, Pinar, additional, Ali, Muhammad Amjad, additional, Wade, James Lloyd, additional, Chien, Amy Jo, additional, Brandt, Debra, additional, Novik, Yelena, additional, Jani, Chirag, additional, Rice, Robert L., additional, Gaffar, Yousuf A. R, additional, Keaton, Mark R., additional, Bajaj, Rajesh, additional, Kimmick, Gretchen, additional, Campbell, David, additional, Turnquest, Theodore, additional, Lucas, Sideras, additional, Dube, Pierre, additional, Xu, Binghe, additional, Schilling, Joerg, additional, Apel, Klaus, additional, Vestlev, Peter Michael, additional, Jensen, Brita Bjerregaard, additional, Haahr, Vera, additional, Lescure, Alvaro Rodriguez, additional, Grana Suarez, Begona, additional, Saura Manich, Cristina, additional, Jacquin, Jean-Philippe, additional, Samreen, Ahmed, additional, Boiangiu, Ion, additional, Dank, Magdolna, additional, Falci, Cristina, additional, Jirillo, Antonio, additional, Cinieri, Saverio, additional, Ueno, Takayuki, additional, Sato, Fumiaki, additional, Yamashiro, Hiroyasu, additional, Sugie, Tomoharu, additional, Lee, Keun Seok, additional, Ro, Jung Sil, additional, Park, In Hae, additional, Bustam, Anita Zarina, additional, Suszko-Kazarnowicz, Malgorzata, additional, Piktel, Artur, additional, Krzemieniecki, Krzysztof, additional, Iorga, Polizenia Georgeta, additional, Yap, Yoon Sim, additional, Kakalejcik, Marian, additional, Sevinc, Alper, additional, Ozguroglu, Mustafa, additional, Chen, Shin-Cheh, additional, Greenberg, Richard H., additional, Eisemann, Allan Daniel, additional, Droder, Robert, additional, Abbasi, M. Rashid, additional, Vaysburd, Marina, additional, Caldera, Humberto Jose, additional, Haley, Barbara Bacsik, additional, Robin, Erwin, additional, Inhorn, Roger C., additional, Hufnagel, David, additional, Kenyon, Peter D., additional, Spremulli, Ellen, additional, Silverman, Paula, additional, Jain, Sharad, additional, Weigand, Robert, additional, Mebis, Jeroen, additional, Koynova, Tatyana, additional, Lesperance, Bernard, additional, Prausova, Jana, additional, Kohne, Claus-Henning, additional, Schneeweiss, Andreas, additional, Jackisch, Christian, additional, Fuxius, Stefan, additional, Cubedo Cervera, Ricardo, additional, Urruticoechea Ribate, Ander, additional, Pernas Simon, Sonia, additional, Valero Gallego, Jose, additional, Arcusa Lanza, Angels, additional, del Pilar Alvarez, Maria, additional, Florian Gerico, Jesus, additional, Cany, Laurent, additional, Stebbing, Justin, additional, Labudovic, Dejan, additional, Gugic, Damir, additional, Vrbanec, Damir, additional, Roila, Fausto, additional, Barni, Sandro, additional, Bidoli, Paolo, additional, Mukai, Hirofumi, additional, Bermudez, Vanessa, additional, Eniu, Alexandru, additional, Mirtsching, Barry C., additional, Ibrahim, Emad, additional, Trey, Joan, additional, Hergenroeder, Paul Francis, additional, Mahmood, Aftab, additional, Gonzalez, Anneliese, additional, Kaplan, Edward H., additional, Ban, Stacy, additional, Patel, Dhimant, additional, Clowney, Billy, additional, Hoelzer, Karen, additional, Schwartz, Garry H., additional, Salkeni, Mohamed, additional, Abraham, Jame, additional, Narula, Sunil, additional, Jabboury, Khaled, additional, Mocharnuk, Robert Scott, additional, McDonough, Richard H., additional, Sikes, David H., additional, Kawanchi, Ronald H., additional, Schlabach, Larry, additional, McCachren, Samuel Spence, additional, Cosgriff, Thomas M., additional, Dreisbach, Luke, additional, DeMichele, Angela, additional, Pawl, Lawrence, additional, Lucas, Jennifer, additional, Shinn, Lowell C., additional, Alkhouri, Nabiel, additional, Monga, Manish, additional, Lindquist, Deborah L., additional, Anderson, Thomas C., additional, Khurshid, Humera, additional, Witherby, Sabrina, additional, Erickson, Nicholette, additional, Traynor, Ann, additional, Bose, Ron, additional, Pluard, Timothy J., additional, Jones, Michael C., additional, Prakash, Sucharu, additional, Volterra, Fabio, additional, Capo, Gerardo, additional, Flaherty, Lawrence E., additional, Gartner, Elaina, additional, Baidas, Said, additional, Okazaki, Ian, additional, Nguyen, Bichlien, additional, Rakowski, Thomas, additional, Oliff, Ira, additional, Leach, Joseph W., additional, Anderson, Daniel, additional, Kubiak, Kendra, additional, Tsai, Michaela, additional, Vroman, Philippe, additional, Deleu, Ines, additional, Lybaert, Willem, additional, Borms, Marleen, additional, Couture, Felix, additional, Wilson, Jonathan J., additional, Hunt, Gordon, additional, Holland, David R., additional, Mingrone, Walter, additional, Wang, Shusen, additional, Liu, Donggeng, additional, Jiang, Zefei, additional, Benesova, Vera, additional, Smakal, Martin, additional, Garnolova, Petra, additional, Vesper, Anne-Sophie, additional, Neumann, Monika, additional, Janni, Wolfgang, additional, Liedtke, Cornelia, additional, Fischer, Dorothea, additional, Grischke, Eva-Maria, additional, Seeger, Dietmar, additional, Moebus, Volker, additional, Prechtl, Anita, additional, Carlos Camara Toral, Juan, additional, Sanchez Munoz, Alfonso, additional, Gonzalez Jimenez, Sonia, additional, Cassinello Espinosa, Javier, additional, Cirauqui, Beatriz, additional, Margeli Vila, Mireia, additional, Batista Lopez, Norberto, additional, Chacon Lopez-Muniz, Jose Ignacio, additional, de la Cruz Mora, Miguel Angel, additional, Mailliez, Audrey, additional, Vanlemmens, Laurence, additional, Pouessel, Damien, additional, Espie, Marc, additional, Conibear, John, additional, Roylance, Rebecca, additional, Harnett, Adrian, additional, Geffen, David, additional, Ruggeri, Enzo Maria, additional, Gamucci, Teresa, additional, Van Groeningen, Cees J., additional, Banas, Renata, additional, Alkis, Necati, additional, Hou, Ming-Feng, additional, Krie, Amy K., additional, Vrindavanam, Nandagopal S., additional, Howard, Orion M., additional, Citrin, Dennis, additional, Morginstin, Mark S., additional, Desai, Ajit, additional, Sanchez, Ines J., additional, Nixon, David Allen, additional, Beatty, Patrick G., additional, Edmiston, Kathryn, additional, McLaughlin, Marilyn, additional, Eneman, Jonathan D., additional, Lynch, Cynthia A., additional, O'Brien, Edward, additional, Call, Justin A., additional, Lanier, Keith S., additional, Conlin, Alison, additional, Brooks, Donald J., additional, McIntyre, Kristi, additional, Saltzman, Marc A., additional, Castine, Michael J., additional, Ortega, Gregory L., additional, Choi, Young M., additional, Reynolds, Craig H., additional, Brescia, Frankie Ann, additional, Kramer, Rita, additional, Kohn, Aimee D., additional, Micha, John P., additional, Rhee, Jessica M., additional, Shah, Satish, additional, Riseberg, David A., additional, Patterson, William Kevin, additional, Salmon, Jean-Paul, additional, Andre, Chantal, additional, Bols, Alain, additional, D'hondt, Randal, additional, Luce, Sylvie, additional, Nouwynck, Claire, additional, Pelgrims, Gino, additional, Richard, Vincent, additional, Verschuere, Johan, additional, Geldhof, Kurt, additional, Caspar, Clemens, additional, Luo, Rongcheng, additional, Bednarik, Otakar, additional, Schwedler, Kathrin, additional, Schmidt, Marcus, additional, Neumeister, Romy, additional, Bischoff, Joachim, additional, Rack, Brigitte, additional, Repp, Roland, additional, Fries, Stefan, additional, Adrion, Ralf, additional, Schulz, Volker, additional, Klare, Peter, additional, Danei, Mahmoud, additional, Ossenbuhl, Dirk, additional, Kusche, Jakob Manfred, additional, Griesinger, Frank, additional, Baena Canada, Jose Manuel, additional, Martinez del Prado, Purificacion, additional, Machover, David, additional, Mayeur, Didier, additional, Trufflandier, Nathalie, additional, Delecroix, Valerie, additional, Mousseau, Mireille, additional, Mouret-Reynier, Marie-Ange, additional, Nabholtz, Jean-Marc, additional, Chetiyawardana, Anula D., additional, Papandreou, Christos, additional, Hornyak, Lajos, additional, Faluhelyi, Zsolt, additional, Simo, Erzsebet, additional, Di Palma, Mario, additional, Cognetti, Francesco, additional, Gorzegno, Gabriella, additional, Dogliotti, Luigi, additional, Gridelli, Cesare, additional, Falcone, Alfredo, additional, Soto Parra, Hector, additional, Buscarino, Calogero, additional, Im, Seock-Ah, additional, Sanchez Llamas, Benito, additional, Dercksen, Wouter, additional, Erdkamp, Franciscus, additional, Ruit, Jan B., additional, Braun, Hans, additional, Portielje, Joanneke E.A., additional, Ciltas, Aydin, additional, Buyukberber, Suleyman, additional, Benekli, Mustafa, additional, Zahalsky, Andrew J., additional, Jaslow, Rebecca, additional, Thomas, Gary W., additional, Maini, Archana, additional, Wiznitzer, Israel, additional, Khojasteh, Ali, additional, Francisco Gonzalez, Manuel, additional, Kong, Lynn R., additional, Padmanabhan, Aruna, additional, Conkright, William A., additional, Swain, Sandra M., additional, Faig, Douglas E., additional, Jain, Kirti, additional, Yanagihara, Ronald H., additional, Ottaviano, Yvonne, additional, Delmas, Andrew, additional, Steele, Heather A., additional, Rainey, Gordon K., additional, Harris, Penelope J., additional, Burris, Jason K., additional, Rupard, Erik J., additional, Tan, Esther, additional, Whitworth, Pat W., additional, Bova, Abby R., additional, Anderson, Ian C., additional, Shirinian, Mihran, additional, Tin-u, Caesar, additional, O'Rourke, Timothy J., additional, Roberts, Michael S., additional, Francisco, Michael, additional, Pierson, A. Scott, additional, Byeff, Peter D., additional, Kovach, Peter A., additional, Caton, John R., additional, Rarick, Mark Urban, additional, Schimidt, William G., additional, Stopeck, Alison T., additional, Swart, Rachel, additional, Carrillo Flores, Maria Regina, additional, Alemany, Carlos A., additional, Lozada, Brennely, additional, Weinstein, Paul L., additional, Wang, Wei, additional, Porubcin, Michael, additional, Ellison, David M., additional, Geils, George F., additional, Rivera, Edgardo, additional, and Charif, Mahmoud, additional

Published
2017
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30. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): An open-label, randomised, controlled phase 3 study

Author

Luis, Paz-Ares, Jörg, Mezger, Tudor E, Ciuleanu, Jürgen R, Fischer, Joachim, von Pawel, Mariano, Provencio, Andrzej, Kazarnowicz, György, Losonczy, Gilberto, de Castro, Aleksandra, Szczesna, Lucio, Crino, Martin, Reck, Rodryg, Ramlau, Ernst, Ulsperger, Christian, Schumann, Jose Elias A, Miziara, Álvaro E, Lessa, Mircea, Dediu, Beatrix, Bálint, Henrik, Depenbrock, Victoria, Soldatenkova, Raffael, Kurek, Fred R, Hirsch, Nick, Thatcher, Mark A, Socinski, and Allan, Price

Subjects
Oncology, Male, medicine.medical_specialty, Guanine, Lung Neoplasms, Time Factors, medicine.medical_treatment, Phases of clinical research, Kaplan-Meier Estimate, Pemetrexed, Antibodies, Monoclonal, Humanized, Disease-Free Survival, Drug Administration Schedule, Glutamates, Risk Factors, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Lung cancer, Necitumumab, Aged, Neoplasm Staging, Cisplatin, Chemotherapy, Intention-to-treat analysis, Performance status, treatment, business.industry, Antibodies, Monoclonal, Middle Aged, medicine.disease, non-small-cell lung cancer, United States, Surgery, Europe, Treatment Outcome, Disease Progression, Female, business, Brazil, medicine.drug
Abstract

Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. We aimed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated, stage IV, non-squamous non-small-cell lung cancer (NSCLC).We did this randomised, open-label, controlled phase 3 study at 103 sites in 20 countries. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function, were randomly assigned 1:1 to treatment with a block randomisation scheme (block size of four) via a telephone-based interactive voice-response system or interactive web-response system. Patients received either cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 of a 3-week cycle for a maximum of six cycles alone, or with necitumumab 800 mg on days 1 and 8. Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects. Randomisation was stratified by smoking history, ECOG performance status, disease histology, and geographical region. Patients and study investigators were not masked to group assignment. The primary endpoint was overall survival. Efficacy analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00982111.Between Nov 11, 2009, and Feb 2, 2011, we randomly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin (n=315) or pemetrexed and cisplatin alone (n=318). Enrolment was stopped on Feb 2, 2011, after a recommendation from the independent data monitoring committee. There was no significant difference in overall survival between treatment groups, with a median overall survival of 11·3 months (95% CI 9·5-13·4) in the necitumumab plus pemetrexed and cisplatin group versus 11·5 months (10·1-13·1) in the pemetrexed and cisplatin group (hazard ratio 1·01 [95% CI 0·84-1·21]; p=0·96). The incidence of grade 3 or worse adverse events, including deaths, was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group; in particular, deaths regarded as related to study drug were reported in 15 (5%) of 304 patients in the necitumumab group versus nine (3%) of 312 patients in the pemetrexed and cisplatin group. Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group (155 [51%] of 304 vs 127 [41%] of 312 patients). Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3-4 rash (45 [15%] of 304 vs one [1%] of 312 patients in the pemetrexed and cisplatin alone group), hypomagnesaemia (23 [8%] vs seven [2%] patients), and grade 3 or higher venous thromboembolic events (23 [8%] vs 11 [4%] patients) than did those in the pemetrexed and cisplatin alone group.Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC. Unless future studies identify potentially useful predictive biomarkers, necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin.Eli Lilly and Company.

Published
2015

32. Safety and Efficacy of Necitumumab (N) During Single-Agent Treatment to Progression Following Gemcitabine-Cisplatin (GC) Chemotherapy Plus Necitumumab (IMC-11F8/LY3012211) in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (sq-NSCLC) (SQUIRE)

Author

Mark A. Socinski, Rodryg Ramlau, Tudor-Eliade Ciuleanu, O. Molinier, Shivani Nanda, B. Balint, Luis Paz-Ares, Coleman K. Obasaju, Andrzej Kazarnowicz, Aleksandra Szczesna, H. Depenbrock, W. Szafranski, Nick Thatcher, and Alexander Luft

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Radiation, business.industry, medicine.medical_treatment, Gemcitabine/cisplatin, First line treatment, Internal medicine, medicine, Squamous non-small cell lung cancer, Radiology, Nuclear Medicine and imaging, Single agent, business, Stage iv, Necitumumab
Published
2014
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33. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): An open-label, randomised, controlled phase 3 trial

Author

Thatcher, N, Hirsch, F, Luft, A, Szczesna, A, Ciuleanu, T, Dediu, M, Ramlau, R, Galiulin, R, Bálint, B, Losonczy, G, Kazarnowicz, A, Park, K, Schumann, C, Reck, M, Depenbrock, H, Nanda, S, Kruljac-Letunic, A, Kurek, R, Paz-Ares, L, Socinski, M, Bidoli, P, Hirsch, FR, Luft, AV, Ciuleanu, TE, Galiulin, RK, Socinski, MA, Thatcher, N, Hirsch, F, Luft, A, Szczesna, A, Ciuleanu, T, Dediu, M, Ramlau, R, Galiulin, R, Bálint, B, Losonczy, G, Kazarnowicz, A, Park, K, Schumann, C, Reck, M, Depenbrock, H, Nanda, S, Kruljac-Letunic, A, Kurek, R, Paz-Ares, L, Socinski, M, Bidoli, P, Hirsch, FR, Luft, AV, Ciuleanu, TE, Galiulin, RK, and Socinski, MA

Abstract

Background: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. Methods: We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m2 administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m2 administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash-a class effect of EGFR antibodies-that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Findings: Between Jan 7, 2010, and Feb 22, 2012, we

Published
2015

34. Safety and efficacy of necitumumab continuation therapy: Subgroup analysis of phase 3 SQUIRE study.

Author

Ciuleanu, Tudor E., primary, Socinski, Mark A., additional, Obasaju, Coleman K., additional, Luft, Alexander, additional, Szczesna, Aleksandra, additional, Szafranski, Wojciech, additional, Ramlau, Rodryg, additional, Bálint, Beatrix, additional, Kazarnowicz, Andrzej, additional, Molinier, Olivier, additional, Depenbrock, Henrik, additional, Nanda, Shivani, additional, Paz-Ares, Luis, additional, and Thatcher, Nick, additional

Published
2015
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35. TG4010 immunotherapy plus chemotherapy as first-line treatment of advanced non small cell lung cancer (NSCLC): Phase IIb results of the TIME trial

Author

Christian H. Ottensmeier, György Losonczy, A. Madroszyk, Frederic Forget, J.T. Beck, Virginie Westeel, Elisabeth Quoix, Alexandra Szczesna, Didier Debieuvre, Z. Papai, Radj Gervais, John Nemunaitis, Hervé Lena, Enriqueta Felip, Jean Marc Limacher, Christos Chouaid, and Andrzej Kazarnowicz

Subjects
Oncology, Cancer Research, medicine.medical_specialty, viruses, medicine.medical_treatment, Immunology, non-small cell lung cancer (NSCLC), chemical and pharmacologic phenomena, Bioinformatics, complex mixtures, Time trial, Immune system, Internal medicine, medicine, Immunology and Allergy, skin and connective tissue diseases, neoplasms, MUC1, Pharmacology, Chemotherapy, business.industry, hemic and immune systems, Immunotherapy, medicine.disease, digestive system diseases, biological factors, First line treatment, Poster Presentation, Molecular Medicine, business
Abstract

Meeting abstracts TG4010 is an immunotherapy using an attenuated and modified poxvirus (MVA) coding for MUC1 and interleukin-2 to induce a cellular immune response against MUC1 expressing tumors. Previous Phase 2 trials have demonstrated the efficacy and safety of TG4010 in combination with

Published
2015

36. Safety and efficacy of necitumumab continuation therapy: Subgroup analysis of phase 3 SQUIRE study

Author

Luis Paz-Ares, Tudor Ciuleanu, Aleksandra Szczesna, Mark A. Socinski, Wojciech Szafranski, Coleman K. Obasaju, Beatrix Bálint, Alexander Luft, Olivier Molinier, Andrzej Kazarnowicz, Rodryg Ramlau, Shivani Nanda, H. Depenbrock, and Nick Thatcher

Subjects
Oncology, Cancer Research, medicine.medical_specialty, business.industry, Improved survival, Subgroup analysis, humanities, Surgery, Continuation, Internal medicine, Squire, Medicine, In patient, business, Stage iv, Necitumumab
Abstract

e19024 Background: The SQUIRE study demonstrated that the addition of necitumumab (N) to gemcitabine-cisplatin (GC) improved survival in patients (pts) with stage IV sq-NSCLC. This retrospective an...

Published
2015
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37. TG4010 immunotherapy plus chemotherapy as first-line treatment of advanced non small cell lung cancer (NSCLC): Phase IIb results of the TIME trial

Author

Nemunaitis, John, primary, Papai, Zsolt, additional, Léna, Hervé, additional, Losonczy, Gyorgy, additional, Forget, Frederic, additional, Chouaid, Christos, additional, Szczesna, Alexandra, additional, Gervais, Radj, additional, Ottensmeier, Christian H, additional, Beck, Joseph, additional, Kazarnowicz, Andrzej, additional, Westeel, Virginie, additional, Debieuvre, Didier, additional, Madroszyk, Anne, additional, Felip, Enriqueta, additional, Limacher, Jean, additional, and Quoix, Elisabeth, additional

Published
2015
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38. TIME, a Phase 2b/3 Study Evaluating TG4010 in Combination With First-Line Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC): Phase 2b Results

Author

Quoix, E., primary, Losonczy, G., additional, Forget, F., additional, Chouaid, C., additional, Papai, Z., additional, Gervais, R., additional, Ottensmeier, C., additional, Szczesna, A., additional, Kazarnowicz, A., additional, Beck, J.T., additional, Westeel, V., additional, Vanderheyde, K., additional, Lacoste, G., additional, Bastien, B., additional, Halluard, C., additional, Marchand, S., additional, Limacher, J.M., additional, and Léna, H., additional

Published
2014
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39. Safety and Efficacy of Necitumumab (N) During Single-Agent Treatment to Progression Following Gemcitabine-Cisplatin (GC) Chemotherapy Plus Necitumumab (IMC-11F8/LY3012211) in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (sq-NSCLC) (SQUIRE)

Author

Socinski, M.A., primary, Thatcher, N., additional, Luft, A.V., additional, Szczesna, A., additional, Ciuleanu, T., additional, Szafrański, W., additional, Ramlau, R., additional, Bálint, B., additional, Kazarnowicz, A., additional, Molinier, O., additional, Depenbrock, H., additional, Nanda, S., additional, Obasaju, C., additional, and Paz-Ares, L., additional

Published
2014
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40. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC).

Author

Thatcher, Nick, primary, Hirsch, Fred R., additional, Szczesna, Aleksandra, additional, Ciuleanu, Tudor-Eliade, additional, Szafranski, Wojciech, additional, Dediu, Mircea, additional, Ramlau, Rodryg, additional, Galiulin, Rinat, additional, Bálint, Beatrix, additional, Losonczy, Gyorgy, additional, Kazarnowicz, Andrzej, additional, Park, Keunchil, additional, Schumann, Christian, additional, Reck, Martin, additional, Paz-Ares, Luis, additional, Depenbrock, Henrik, additional, Nanda, Shivani, additional, Kruljac-Letunic, Anamarija, additional, and Socinski, Mark A., additional

Published
2014
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41. TIME, a Phase 2b/3 Study Evaluating TG4010 in Combination With First-Line Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC): Phase 2b Results

Author

Frederic Forget, Virginie Westeel, Bérangère Bastien, Céline Halluard, Radj Gervais, Z. Papai, Gisèle Lacoste, Christos Chouaid, Aleksandra Szczesna, E. Quoix, Andrzej Kazarnowicz, S. Marchand, K. Vanderheyde, Hervé Lena, Christian H. Ottensmeier, György Losonczy, J.T. Beck, and Jean-Marc Limacher

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Radiation, business.industry, Phase (waves), non-small cell lung cancer (NSCLC), medicine.disease, First line therapy, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, business
Published
2014
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42. Time, a Phase 2B/3 Study Evaluating Tg4010 in Combination with First Line Therapy in Advanced Non Small Cell Lung Cancer (Nsclc). Phase 2B Results

Author

Bérangère Bastien, György Losonczy, Annette Tavernaro, Enriqueta Felip, Christian H. Ottensmeier, Aleksandra Szczesna, J.T. Beck, Z. Papai, Anne Madroszyk, E. Quoix, Jean-Marc Limacher, Gisèle Lacoste, Frederic Forget, Virginie Westeel, Didier Debieuvre, Radj Gervais, T. Palanche, Hervé Lena, Christos Chouaid, and Andrzej Kazarnowicz

Subjects
Oncology, medicine.medical_specialty, Performance status, business.industry, Hazard ratio, non-small cell lung cancer (NSCLC), Hematology, medicine.disease, Chemotherapy regimen, Surgery, Response Evaluation Criteria in Solid Tumors, Aldesleukin, Internal medicine, medicine, Clinical endpoint, Progression-free survival, business
Abstract

Aim: TG4010 immunotherapy product is a poxvirus (MVA) coding for MUC1 tumor-associated antigen and interleukin-2. A previous study showed that a normal baseline level of Triple Positive Activated Lymphocytes (TrPAL, CD16 + CD56 + CD69+) might be a predictive biomarker for TG4010 efficacy in NSCLC (Lancet Oncol 2011;12:1125-33). TIME is a double-blind phase 2b/3 study (NCT01383148) comparing the combination of first line therapy with TG4010 or placebo. The Phase 2b part aims at prospectively validating the baseline TrPAL level as a predictive biomarker. Methods: Primary endpoint of the Phase 2b part of the study was to compare progression-free survival (PFS, according to RECIST 1.1) between TG4010 and placebo arms using a Bayesian design, in stage IV NSCLC patients with a MUC1+ tumor. Secondary objectives were response rate, safety, survival and subgroup analyses. A dynamic minimization procedure was applied at randomization for histology, prescription of bevacizumab, type of chemotherapy, performance status and center. Results: 217 patients have been enrolled out of which 170 patients with a normal TrPAL level (pre-determined threshold) and an analysis of PFS was conducted in this cohort after 137 events of progression were recorded. The hazard ratio (HR) for PFS is 0.76 (95%CI: 0.54-1.06). This corresponds to a 97.5% Bayesian probability that the true HR is Conclusions: These data support the predictive value of the TrPAL biomarker. They also confirm TG4010 efficacy and safety profile in stage IV NSCLC patients and warrant the continuation of the TIME study with its Phase 3 part. Disclosure: E. Quoix: Transgene: joint steering committee member and consultant; C. Chouaid: Consultant for Lilly, GSK, Amgen Advisory board member: Lilly, Roche, AZ, Amgen, Boheringer Ingelheim; Z. Papai: Advisory board member for Transgene; V. Westeel: Advisory board member for Roche, Lilly. Honoraria from Astra Zeneca, Boehringer, Teva; G. Lacoste: Transgene employee. Stockoption ownership; A. Tavernaro: Transgene employee. Stockoption ownership; B. Bastien: Transgene employee. Stockoption ownership; T. Palanche: Transgene employee with Transgene stock options; J. Limacher: Transgene employee. Stock option owner. All other authors have declared no conflicts of interest.

Published
2014
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43. A randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin (GC) chemotherapy plus necitumumab (IMC-11F8/LY3012211) versus GC alone in the first-line treatment of patients (pts) with stage IV squamous non-small cell lung cancer (sq-NSCLC)

Author

H. Depenbrock, György Losonczy, Andrzej Kazarnowicz, Luis Paz-Ares, Mark A. Socinski, Wojciech Szafranski, Rodryg Ramlau, Mircea Dediu, Anamarija Kruljac-Letunic, Nick Thatcher, Rinat Galiulin, Christian Schumann, Beatrix Bálint, Shivani Nanda, Tudor-Eliade Ciuleanu, Keunchil Park, Aleksandra Szczesna, Martin Reck, and Fred R. Hirsch

Subjects
Oncology, Cancer Research, Chemotherapy, medicine.medical_specialty, medicine.drug_class, business.industry, medicine.medical_treatment, Gemcitabine/cisplatin, Monoclonal antibody, First line treatment, Internal medicine, medicine, Squamous non-small cell lung cancer, Open label, Stage iv, business, Necitumumab
Abstract

8008^ Background: Necitumumab (N), a human IgG1 anti-EGFR monoclonal antibody, inhibits ligand-binding and receptor activation. EGFR is detectable in the vast majority of advanced sq-NSCLC tumors. ...

Published
2014
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44. A randomized phase II study of carboplatin (C) and etoposide (E) with or without pan-BCL-2 antagonist obatoclax (Ob) in extensive-stage small cell lung cancer (ES-SCLC).

Author

Langer, C. J., primary, Albert, I., additional, Kovacs, P., additional, Blakely, L. J., additional, Pajkos, G., additional, Petrov, P., additional, Somfay, A., additional, Szczesna, A., additional, Zatloukal, P., additional, Kazarnowicz, A., additional, Moezi, M. M., additional, Schreeder, M. T., additional, Schnyder, J., additional, and Berger, M. S., additional

Published
2011
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48. Why they want to be treated in clinical trial -fundamental reasons of patient's decision

Author

E. Wachula, S. Szablowska-Siwik, M. Czerniawska, A. Kazarnowicz, and A. I. Jagiello-Gruszfeld

Subjects
Clinical trial, Cancer Research, medicine.medical_specialty, Oncology, business.industry, Family medicine, Medicine, business
Abstract

6147 Background: Today, in oncological treatment most of patients are treating with new agents in clinical trials. For every one making decision of taking part in that study is not so easy. In new ...

Published
2004
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50. The role of neoadjuvant treatment with combination of docetaxel and doxorubicin for breast cancer patients

Author

M. Krzakowski, M. Foszczynska-Kloda, M. Suszko-Kazarnowicz, K. Drosik, J. Zaluski, B. Kaczmarek-Borowska, E. Filipczuk-Cirsaz, B. Liszka, Agnieszka Jagiełło-Gruszfeld, and Tadeusz Pienkowski

Subjects
Oncology, medicine.medical_specialty, business.industry, General Medicine, medicine.disease, Breast cancer, Docetaxel, Neoadjuvant treatment, Internal medicine, medicine, Surgery, Doxorubicin, business, medicine.drug
Published
2003
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