Search

Your search keyword '"Sabanathan Dhanusha"' showing total 30 results
Start Over Author "Sabanathan Dhanusha"
30 results on '"Sabanathan Dhanusha"'

4. 614 Safety and efficacy of YBL-006, a novel anti-PD-1 antibody, in advanced solid tumors including G3 NET/NEC: results from a phase 1/2A study

Author

Lee, Keun-Wook, primary, Park, John, additional, Kim, Seung-Tae, additional, Sriuranpong, Virote, additional, Rha, Sun Young, additional, Yoo, Changhoon, additional, Kim, Sehyun, additional, Keam, Bhumsuk, additional, Sabanathan, Dhanusha, additional, Park, Joon Oh, additional, Parinyanitikul, Napa, additional, Kim, Min Hwan, additional, Kim, Kyu Pyo, additional, Ock, Chan-Young, additional, Yoon, Jaebong, additional, Lim, Hyelim, additional, Lee, Sangheon, additional, Jang, Wooick, additional, and Oh, Do-Youn, additional

Published
2023
Full Text
View/download PDF

9. Safety and efficacy of YBL-006, an anti-PD-1 monoclonal antibody in advanced solid tumors: A phase I study.

Author

Oh, Do-Youn, primary, Park, John J., additional, Lee, Keun Wook, additional, Kim, Seung Tae, additional, Sriuranpong, Virote, additional, Rha, Sun Young, additional, Yoo, Changhoon, additional, Keam, Bhumsuk, additional, Sabanathan, Dhanusha, additional, Kim, Se Hyun, additional, Park, Joon Oh, additional, Parinyanitikul, Napa, additional, Kim, Min Hwan, additional, Kim, Kyu-Pyo, additional, Kim, Myungsuk, additional, Yoon, Jaebong, additional, Lee, Han Seung, additional, and Ock, Chan-Young, additional

Published
2022
Full Text
View/download PDF

10. KEYNOTE-B49: A phase 3, randomized, double-blind, placebo-controlled study of pembrolizumab plus chemotherapy in patients with HR+/HER2- locally recurrent inoperable or metastatic breast cancer.

Author

Rugo, Hope S., primary, Sohn, Joohyuk, additional, Jerez Gilarranz, Yolanda, additional, Gonzalez-Cortijo, Lucia, additional, Sonnenblick, Amir, additional, Sabanathan, Dhanusha, additional, Korbenfeld, Ernesto Pablo, additional, Egle, Daniel, additional, Poirier, Brigitte, additional, Zagouri, Flora, additional, Matikas, Alexios, additional, Aksoy, Sercan, additional, Demirci, Umut, additional, Ramos-Elias, Pier, additional, Im, Seock-Ah, additional, Cardoso, Fatima, additional, Jia, Liyi, additional, Baccan, Carlos, additional, Tryfonidis, Konstantinos, additional, and Schmid, Peter, additional

Published
2022
Full Text
View/download PDF

11. Abstract P4-12-01: Adherence with adjuvant endocrine therapy with or without Palbociclib in the PALLAS trial

Author

Shinn, Eileen, primary, Zahrieh, David, additional, DeMichele, Angela, additional, Zdenkowski, Nick, additional, Lemieux, Julie, additional, Mao, Jun, additional, Bjelic-Radisic, Vesna, additional, Naughton, Michelle, additional, Pfeiler, Georg, additional, Gelmon, Karen, additional, Mayer, Ingrid, additional, Egle, Daniel, additional, Zoppoli, Gabriele, additional, Traina, Tiffany, additional, Jiménez, Miguel Martin, additional, Novoa, Silvia Antolin, additional, Haddad, Tufia, additional, Chan, Arlene, additional, Ring, Alistair Edward, additional, Wolff, Antonio, additional, Lorenzo, Jose JuanPonce, additional, Sabanathan, Dhanusha, additional, Burstein, Hal, additional, Nowecki, Zbigniew Ireneusz, additional, Pristauz-Telsnigg, Gunda, additional, Brufsky, Adam, additional, Bellet-Ezquerra, Meritxell, additional, Foukakis, Theodoros, additional, Novik, Yelena, additional, Rubovszky, Gabor, additional, Muehlbacher, Karoline, additional, Metzger, Otto, additional, Goulioti, Theodora, additional, Law, Ernest, additional, Partridge, Ann, additional, Carey, Lisa, additional, Zoroufy, Alex, additional, Hlauschek, Dominik, additional, Fesl, Christian, additional, Mayer, Erica, additional, and Gnant, Michael, additional

Published
2022
Full Text
View/download PDF

12. Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03)

Author

Mayer, Erica L., primary, Fesl, Christian, additional, Hlauschek, Dominik, additional, Garcia-Estevez, Laura, additional, Burstein, Harold J., additional, Zdenkowski, Nicholas, additional, Wette, Viktor, additional, Miller, Kathy D., additional, Balic, Marija, additional, Mayer, Ingrid A., additional, Cameron, David, additional, Winer, Eric P., additional, Ponce Lorenzo, José Juan, additional, Lake, Diana, additional, Pristauz-Telsnigg, Gunda, additional, Haddad, Tufia C., additional, Shepherd, Lois, additional, Iwata, Hiroji, additional, Goetz, Matthew, additional, Cardoso, Fatima, additional, Traina, Tiffany A., additional, Sabanathan, Dhanusha, additional, Breitenstein, Urs, additional, Ackerl, Kerstin, additional, Metzger Filho, Otto, additional, Zehetner, Karin, additional, Solomon, Kadine, additional, El-Abed, Sarra, additional, Theall, Kathy Puyana, additional, Lu, Dongrui Ray, additional, Dueck, Amylou, additional, Gnant, Michael, additional, and DeMichele, Angela, additional

Published
2022
Full Text
View/download PDF

13. Safety and tolerability of Miltuximab(®) - a first in human study in patients with advanced solid cancers

Author

Sabanathan, Dhanusha, Campbell, Douglas H., Velonas, Vicki M., Wissmueller, Sandra, Mazure, Hubert, Trifunovic, Marko, Poursoltan, Pirooz, Ho Shon, Kevin, Mackay, Tiffany R., Lund, Maria E., Lu, Yanling, Roach, Paul J., Bailey, Dale L., Walsh, Bradley J., Gillatt, David, and Gurney, Howard

Subjects
Original Article
Abstract

OBJECTIVE(S): Miltuximab(®) is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab(®) has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab(® )radiolabelled with Gallium-67 ([(67)Ga]Ga-DOTA-Miltuximab(®)). The primary study endpoint was to establish safety and tolerability of Miltuximab(®). Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis. METHODS: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [(67)Ga]Ga-DOTA-Miltuximab(®). Cohort 1 received [(67)Ga]Ga-DOTA-Miltuximab(®) alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab(®)-DOTA 1 hour prior to [(67)Ga]Ga-DOTA-Miltuximab(®). Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans. RESULTS: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [(67)Ga]Ga-DOTA-Miltuximab(®) was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab(®)-DOTA. Dosimetry analysis showed a favorable exposure profile. [(67)Ga]Ga-DOTA-Miltuximab(®) targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life. CONCLUSIONS: This study is the first in human for Miltuximab(®) a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab(®) as a theranostic agent in a planned Phase I human trial.

Published
2021

14. Interim analysis of first-in-human phase 1 study to assess safety and efficacy of YBL-006, an anti-PD-1 antibody in advanced solid tumor with exploratory biomarker analysis of tumor mutational burden and artificial intelligence (AI)-powered spatial analysis of tumor-infiltrating lymphocytes.

Author

Park, John J., primary, Lee, Keun Wook, additional, Oh, Do-Youn, additional, Sabanathan, Dhanusha, additional, Kim, Se Hyun, additional, Kim, Tae Min, additional, Kim, Myungsuk, additional, Yoon, Jaebong, additional, Lee, Hyunmi, additional, Kim, Boram, additional, Ko, Yunjung, additional, Jeon, Eunyoung, additional, Cheon, Seonghye, additional, Shim, Eunyoung, additional, Park, Bum-Chan, additional, Lee, Han Seung, additional, Park, Seongyeol, additional, Paeng, Kyunghyun, additional, and Ock, Chan-Young, additional

Published
2021
Full Text
View/download PDF

15. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author

Amgad, Mohamed, Stovgaard, Elisabeth Specht, Balslev, Eva, Thagaard, Jeppe, Chen, Weijie, Dudgeon, Sarah, Sharma, Ashish, Kerner, Jennifer K., Denkert, Carsten, Yuan, Yinyin, AbdulJabbar, Khalid, Wienert, Stephan, Savas, Peter, Voorwerk, Leonie, Beck, Andrew H., Madabhushi, Anant, Hartman, Johan, Sebastian, Manu M., Horlings, Hugo M., Hudeček, Jan, Ciompi, Francesco, Moore, David A., Singh, Rajendra, Roblin, Elvire, Balancin, Marcelo Luiz, Mathieu, Marie-Christine, Lennerz, Jochen K., Kirtani, Pawan, Chen, I-Chun, Braybrooke, Jeremy P., Pruneri, Giancarlo, Demaria, Sandra, Adams, Sylvia, Schnitt, Stuart J., Lakhani, Sunil R., Rojo, Federico, Comerma, Laura, Badve, Sunil S., Khojasteh, Mehrnoush, Symmans, W. Fraser, Sotiriou, Christos, Gonzalez-Ericsson, Paula, Pogue-Geile, Katherine L., Kim, Rim S., Rimm, David L., Viale, Giuseppe, Hewitt, Stephen M., Bartlett, John M. S., Penault-Llorca, Frédérique, Goel, Shom, Lien, Huang-Chun, Loibl, Sibylle, Kos, Zuzana, Loi, Sherene, Hanna, Matthew G., Michiels, Stefan, Kok, Marleen, Nielsen, Torsten O., Lazar, Alexander J., Bago-Horvath, Zsuzsanna, Kooreman, Loes F. S., van der Laak, Jeroen A. W. M., Saltz, Joel, Gallas, Brandon D., Kurkure, Uday, Barnes, Michael, Salgado, Roberto, Cooper, Lee A. D., Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Gown, Allen, Lo, Amy, Sapino, Anna, Moreira, Andre, Richardson, Andrea, Vingiani, Andrea, Bellizzi, Andrew M., Tutt, Andrew, Guerrero-Zotano, Angel, Grigoriadis, Anita, Ehinger, Anna, Garrido-Castro, Anna C., Vincent-Salomon, Anne, Laenkholm, Anne-Vibeke, Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Castaneda, Carlos, Ballesteroes-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Swanton, Charles, Solinas, Cinzia, Hiley, Crispin, Drubay, Damien, Bethmann, Daniel, Dillon, Deborah A., Larsimont, Denis, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Brogi, Edi, Perez, Edith, ElGabry, Ehab A., Blackley, Elizabeth F., Reisenbichler, Emily, Bellolio, Enrique, Chmielik, Ewa, Gaire, Fabien, Andre, Fabrice, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Gruosso, Forbius Tina, Peale, Franklin, Hirsch, Fred R., Klaushen, Frederick, Acosta-Haab, Gabriela, Farshid, Gelareh, van den Eynden, Gert, Curigliano, Giuseppe, Floris, Giuseppe, Broeckx, Glenn, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Cree, Ian, Nederlof, Iris, Frahm, Isabel, Brcic, Iva, Chan, Jack, Hall, Jacqueline A., Ziai, James, Brock, Jane, Wesseling, Jelle, Giltnane, Jennifer, Lemonnier, Jerome, Zha, Jiping, M. Ribeiro, Joana, Carter, Jodi M., Hainfellner, Johannes, Quesne, John Le, Juco, Jonathan W., Reis-Filho, Jorge, van den Berg, Jose, Sanchez, Joselyn, Sparano, Joseph, Cucherousset, Joël, Araya, Juan Carlos, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Willard-Gallo, Karen, Sikorska, Karolina, Weber, Karsten, Steele, Keith E., Emancipator, Kenneth, El Bairi, Khalid, Blenman, Kim R. M., Allison, Kimberly H., van de Vijver, Koen K., Korski, Konstanty, Pusztai, Lajos, Buisseret, Laurence, Shi, Leming, Shi-wei, Liu, Molinero, Luciana, Estrada, M. Valeria, van Seijen, Maartje, Lacroix-Triki, Magali, Cheang, Maggie C. U., Bakir, Maise al, van de Vijver, Marc, Dieci, Maria Vittoria, Rebelatto, Marlon C., Piccart, Martine, Goetz, Matthew P., Preusser, Matthias, Sanders, Melinda E., Regan, Meredith M., Christie, Michael, Misialek, Michael, Ignatiadis, Michail, de Maaker, Michiel, van Bockstal, Mieke, Castillo, Miluska, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Jelinic, Petar, Watson, Peter H., Francis, Prudence A., Russell, Prudence A., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, de Wind, Roland, Shui, Ruohong, Declercq, Sabine, Leung, Sam, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Willis, Scooter, Ely, Scott, Kim, Seong- Rim, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shi-Wei, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Fox, Stephen B., Luen, Stephen J., Naber, Stephen, Luz, Sua, Fineberg, Susan, Soler, Teresa, Gevaert, Thomas, d’Alfons, Timothy, John, Tom, Sugie, Tomohagu, Bossuyt, Veerle, Manem, Venkata, Cámaea, Vincente Peg, Tong, Weida, Yang, Wentao, Tran, William T., Wang, Yihong, Allory, Yves, Husain, Zaheed, Amgad, Mohamed [0000-0001-7599-6162], Sharma, Ashish [0000-0002-1011-6504], Savas, Peter [0000-0001-5999-428X], Hudeček, Jan [0000-0003-1071-5686], Braybrooke, Jeremy P. [0000-0003-1943-7360], Demaria, Sandra [0000-0003-4426-0499], Comerma, Laura [0000-0002-0249-4636], Badve, Sunil S. [0000-0001-8861-9980], Symmans, W. Fraser [0000-0002-1526-184X], Gonzalez-Ericsson, Paula [0000-0002-6292-6963], Rimm, David L. [0000-0001-5820-4397], Loi, Sherene [0000-0001-6137-9171], Hanna, Matthew G. [0000-0002-7536-1746], Lazar, Alexander J. [0000-0002-6395-4499], Bago-Horvath, Zsuzsanna [0000-0002-8555-7806], van der Laak, Jeroen A. W. M. [0000-0001-7982-0754], Gallas, Brandon D. [0000-0001-7332-1620], Kurkure, Uday [0000-0002-8273-7334], Cooper, Lee A. D. [0000-0002-3504-4965], and Apollo - University of Cambridge Repository

Subjects
631/67/580, 692/4028/67/1857, 631/67/2321, 692/53/2422, review-article, Review Article, 631/67/1347
Abstract

Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

Published
2020

16. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial

Author

Vassiliki Karantza, Shparyk Yaroslav, Sumrall Bradley, Javier Cortes, Iwata Hiroji, Kolesnik Oleksii, Ahn Jin Hee, Harbeck Nadia, Prausova Jana, Song Xinni, Berzoy Oleksandr, Mena Raul, Osaki Akihiko, Kahan Zsuzsanna, Simon Michael, Ozguroglu Mustafa, Chmielowska Ewa, Tsugawa Koichiro, Tsao Chao-Jung, Ozyilkan Ozgur, Nowecki Zbigniew, Fadeeva Natalia, Kaen Diego, Garcia Saenz Jose, Porter David, Ngan Kai Cheong Roger, Sherene Loi, Bermejo de las Heras Begona, Turner Nicholas, David W. Cescon, Hope S. Rugo, Oliff Ira, Kelly Catherine, Barrios Carlos, Cole Scott, Shevnya Sergii, Seock-Ah Im, Hoskins Kent, Komisarenko Hanna, Yavuz Sinan, Chaudhry Madhu, Sagara Yasuaki, Brust Leandro, Chan Steve, Gomez Villanueva Angel, Gallardo Carlos, Watanabe Junichiro, Ishikawa Takashi, Schleider Michael, Salas Claudio, Hardy-Bessard Anne-Claire, Erhan Gokmen, Adamchuk Hryhoriy, Beelen Karin, Holeckova Petra, Szczylik Cezary, Fujii Takaaki, Nakamura Seigo, Aruga Tomoyuki, Gokmen Erhan, Jing Zhao, Hiroji Iwata, Molinas Mandel Nil, Gogineni Keerthi, Im Seock-Ah, Zifang Guo, Loi Sherene, Costa Fabiano, Forstmeyer Dirk, Kosaka Yoshimasa, Gomez Diaz Alvaro, Ponomarova Olga, Wimberger Pauline, DAlessio Antonietta, Suzuki Eiji, Blohmer Jens-Uwe, Kowalwszyn Ruben, Molina Matias, Clingan Philip, Yamamoto Yutaka, Sabanathan Dhanusha, Gursel Aktan, Vynnychenko Ihor, Ferrario Cristiano, Schumann Raquel Von, Trukhin Dmytro, Arkosy Peter, Tseng Ling-Ming, Moore Susan, Gunduz Seyda, Stampleman Laura, de Freitas Junior Ruffo, Acevedo Alejandro, Lipatov Oleg, Niikura Naoki, Norikazu Masuda, Rusyn Andrii, Kral Zdenek, Crown John, Yamamoto Naohito, Jakobsen Erik, Blau Sibel, Bustam Anita, Zamora Adelantado Esther, Nanda Rita, Omene Coral, Arslan Cagatay, Kwong Ava, Teixeira Luis, Jensen Jeanette, Ito Yoshinori, Siegel Robert, Mastura Md Yusof, Nowakowska-Zajdel Ewa, Miyoshi Yasuo, Yu Joanne, Tuthill Mark, Mukhametshina Guzel, Matsumoto Koji, Gion Maria, Melichar Bohuslav, Desmoulins Isabelle, Moiseyenko Vladimir, Zurawski Bogdan, Carlos Gallardo, Lorincz Tamas, Cruz Jurado Josefina, Bondarenko Igor, Kaczerowsky Flores de Sousa Anna, Yamauchi Teruo, Loutfi Randa, Esther Holgado, Holgado Esther, Twelves Christopher, Streb Joanna, Tanabe Yuko, Tarnawski Rafal, Morales-Vasquez Flavia, Park Kwong Hwa, Csoszi Tibor, Meshcheryakov Andrey, Scalabrini Neto Antonio Orlando, Oleg Lipatov, Iwasa Tsutomu, Ricevuto Enrico, Tamura Kenji, Patson Brian, Liu Mei-Ching, Cinieri Saverio, Loibl Sibylle, Tjan-Heijnen Vivianne, Glavicic Vesna, Panwalkar Amit, Hargis Jeffrey, Kryzhanivska Anna, Yusof Mastura, O'Reilly Seamus, Rubovszky Gabor, Irvin William, Takahashi Masato, Ohtani Shoichiro, Peter Schmid, Carlos H. Barrios, Sanchez Cesar, Zbigniew Nowecki, Arkhipov Alexander, Chung Michael, Liu Chien-Ting, Mukai Hirofumi, Marco Torregroza Otero, Charpentier Danielle, Park-Simon Tjoung-Won, Lee Keun Seok, Leshchenko Iurii, Huang Chiun-Sheng, Tsai Michaela, Panella Timothy, Petrakova Katarina, MacPherson Iain, Schmid Peter, Baron-Hay Sally, Ursol Grygorii, Lacerda Domicio Carvalho, Cobb Patrick, Sanchez Jesus, Park Yeon Hee, Reyes Contreras Jessica, Fein Luis, Hegg Roberto, Diamond Jennifer, Huober Jens, Rugo Hope, Rybalova Irina, de la Cruz Merino Luis, Linnet Soren, Inoue Kenichi, Wheatley Duncan, Cescon David, Cicin Irfan, Gombos Andrea, Bonnefoi Herve, Nasonova Alla, Taylor Donatienne, Martinez Rodriguez Jorge, Valdes-Albini Frances, Juarez Ramiro Alejandro, Cortes Javier, Lu Janice, Silva Felipe, Lueftner Diana, Landherr Laszlo, Gomez Abuin Gonzalo, Yanez Eduardo, Rocha Roberto Odebrecht, Chow Louis, Otchenash Natalya, Radecka Barbara, Kolesnik Olena, Basaran Gul, Kurbacher Christian, Mahr Karoly, Goncalves Anthony, Begbie Stephen, Graham Janine, Fasching Peter, Varela Mirta, and Lissa Fernando Cezar Toniazzi

Subjects
Oncology, double blind procedure, pharmacist, CD274 protein, human, hazard ratio, 0302 clinical medicine, middle aged, Antineoplastic Combined Chemotherapy Protocols, cancer survival, comparative study, education.field_of_study, progression free survival, adult, drug effect, gemcitabine, clinical trial, General Medicine, nausea, anemia, Progression-Free Survival, priority journal, immunological antineoplastic agent, thyroiditis, pembrolizumab, metastatic breast cancer, neoadjuvant chemotherapy, medicine.medical_specialty, Antineoplastic Agents, intention to treat analysis, Article, skin manifestation, 03 medical and health sciences, Breast cancer, cancer combination chemotherapy, neutropenia, Humans, Progression-free survival, human, education, protein expression, cancer immunotherapy, treatment response, Interim analysis, medicine.disease, major clinical study, tumor recurrence, Carboplatin, programmed death 1 ligand 1, drug efficacy, multicenter study, chemistry, monoclonal antibody, randomized controlled trial, fatigue, drug tolerability, cancer patient, age distribution, drug safety, colitis, clinical outcome, Triple Negative Breast Neoplasms, Pembrolizumab, 030204 cardiovascular system & hematology, B7-H1 Antigen, Placebos, chemistry.chemical_compound, paclitaxel, Antineoplastic Agents, Immunological, Outcome Assessment, Health Care, 030212 general & internal medicine, antineoplastic agent, cancer adjuvant therapy, Eastern Cooperative Oncology Group performance status, female, carboplatin, sodium chloride, immunohistochemistry, medicine.drug, interactive voice response system, alanine aminotransferase, overall survival, Population, Antibodies, Monoclonal, Humanized, Double-Blind Method, Internal medicine, medicine, follow up, hyperthyroidism, pneumonia, controlled study, Taxane, phase 3 clinical trial, business.industry, hypertransaminasemia, alopecia, Gemcitabine, human tissue, cancer recurrence, functional status assessment, triple negative breast cancer, placebo, inoperable cancer, pathology, hypothyroidism, Neoplasm Recurrence, Local, business, metabolism, Follow-Up Studies
Abstract

Background: Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer. Methods: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine–carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ?1 or, Breast Cancer Research Foundation, BCRF; Pfizer; AstraZeneca; Merck; Roche; Samsung; Merck Sharp and Dohme, MSD; Eisai, JC reports personal fees and research funding paid to his institution from Roche, AstraZeneca, Merck Sharp & Dohme, and Eisai; personal fees from Celgene, Cellestia, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, GlaxoSmithKline, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Kyowa Kirin, Novartis, Pfizer, Samsung Bioepis; research funding paid to his institution from Ariad Pharmaceuticals, Bayer Healthcare, F Hoffman-La Roche, Guardanth Health, Piqur Therapeutics, Puma C, and Queen Mary University of London, outside the submitted work. In addition, JC has a MedSIR patent pending. DWC reports research support from Merck during the conduct of the study; research support paid to his institution from Merck, Pfizer, and GlaxoSmithKline; personal fees from Merck, Roche–Genentech, AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Puma, Agenda, Exact Sciences, and Dynamo Therapeutics, outside the submitted work. In addition, DWC has a Biomarkers of TTK inhibitors patent pending. HSR reports funding for sponsored studies paid to the University of California San Francisco from Pfizer, Novartis, Lilly, Roche–Genentech, Macrogenics, OBI, Merck, Eisai, Immunomedics, Daiichi Sankyo, Seattle Genetics, and Odonate; travel support for educational meetings from Daiichi Sankyo, Mylan, Pfizer, Merck, AstraZeneca, Novartis, and Macrogenics; and consulting fees from Samsung and Puma, outside the submitted work. S-AI reports grants from AstraZeneca, Eisai, Pfizer, Roche, and Daewoong; an advisory role for AstraZeneca, Amgen, Eisai, Hanmi, Novartis, Lily, MedPacto, Pfizer, and Roche; and travel expenses for presentation from Novartis, outside the submitted work. CG reports Advisory Board fees from Merck Sharp & Dohme and Roche; and speaker's bureau fees from Bristol Myers Squibb and AstraZeneca, outside the submitted work. CHB reports grants and fees from Merck Sharp & Dohme for clinical research consulting during the conduct of the study; consulting–advisory role fees from Boehringer Ingelheim, GlaxoSmithKline, and Bayer; consulting–advisory role fees and grants for clinical research from Novartis, Pfizer, Roche–Genentech, Eisai, Merck Sharp & Dohme, and AstraZeneca; grants for clinical research from Abbvie, Amgen, Astellas Pharma, Bristol Myers Squibb, Celgene, Covance, Lilly, Medication, Merck Serono, and PharmaMar; grants for academic research projects from CPO, Pontificia Universidade Católica do Rio Grande do Sul, Latin American Cooperative Oncology Group, Grupo Brasileiro Estudos Câncer Mama, and Instituto Nacional de Câncer-Brazil, outside the submitted work. HI reports a grant from Merck Sharp & Dohme during the conduct of the study; honoraria and consulting fees from Novartis, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Eisai, and Chugai; and a grant from Chugai, outside the submitted work. NM reports honoraria and research funding paid to his institution from Chugai, AstraZeneca, Pfizer, Eli-Lilly, Eisai, Takeda, Kyowa-Kirin, Merck Sharp & Dohme, Novartis, and Daiichi Sankyo, outside the submitted work. EG reports non-financial support from Merck Sharp & Dohme during the conduct of the study; honoraria, consulting–advisory fees and meeting support from Novartis, Roche, Bristol Myers Squibb, and Pfizer; and honoraria from AstraZeneca and Astellas, outside the submitted work. SL reports research funding or consulting fees paid to her institution from Bristol Myers Squibb, Roche–Genentech, Puma Biotechnology, Pfizer, Seattle Genetics, Novartis, Merck Sharp & Dohme, Eli Lilly, Aduro Biotech, GI Therapeutics, AstraZeneca, and GlaxoSmithKline; and non-remunerated consultancy for Bristol Myers Squibb, Roche–Genentech, Pfizer, Seattle Genetics, Novartis, Merck Sharp & Dohme, and AstraZeneca, outside the submitted work. In addition, SL is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. ZG, JZ, GA, and VK are employees of Merck Sharp & Dohme and own stock or stock options in Merck. PS reports consultancy fees from Pfizer, AstraZeneca, Novartis, Roche, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Eisai, Celgene, and Puma; consultancy fees to his spouse from Genentech and Roche; and grants or funding to his institution from Roche, Genentech, Oncogenex, Novartis, Astellas, and AstraZeneca, outside the submitted work. All other authors declare no competing interests., The authors thank the patients, their families and caregivers for participating in this trial, all of the investigators and site personnel, and the following employees of Merck Sharp & Dohme: Wilbur Pan, Deborah Card, Eleanor Readinger, Shana Hamm, Roger Maxwell, and Krystal Bourdon, for collection of data, supervision of research, provision of study materials or patients or administrative or logistical support; Aline Galvao, for collection of data, supervision of research, administrative or logistical support, and review of imaging data related to the primary end point; Donna Letizia, for collection of data and imaging expertise; Jennifer Kimmel, for study management; Mercedes Bustamante, for data collection and management; Xuan Zhou and Madhusudhan Reddy Papasani, for statistical expertise; Christine McCrary Sisk, for medical writing and editorial assistance; and Joseph C Naggar and Michele McColgan, for administrative or logistical support.

Published
2020

20. RetroSPECT: Gallium-67 as a Long-Lived Imaging Agent for Theranostics.

Author

Bailey, Dale L., Sabanathan, Dhanusha, Aslani, Alireza, Campbell, Douglas H., Walsh, Bradley J., and Lengkeek, Nigel A.

Subjects
*RADIONUCLIDE imaging, *COMPANION diagnostics, *BRANCHING ratios, *GAMMA rays, *SCINTILLATION cameras, *NUCLEAR medicine, *RADIATION dosimetry
Abstract

A limitation to the wider introduction of personalised dosimetry in theranostics is the relative paucity of imaging radionuclides with suitable physical and chemical properties to be paired with a long-lived therapeutic partner. As most of the betaemitting therapeutic radionuclides emit gamma radiation as well they could potentially be used as the imaging radionuclide as well as the therapeutic radionuclide. However, the downsides are that the beta radiation will deliver a significant radiation dose as part of the treatment planning procedure, and the gamma radiation branching ratio is often quite low. Gallium-67 has been in use in nuclear medicine for over 50 years. However, the tremendous interest in gallium imaging in theranostics in recent times has focused on the PET radionuclide gallium-68. In this article it is suggested that the longer-lived gallium-67, which has desirable characteristics for imaging with the gamma camera and a suitably long half-life to match biological timescales for drug uptake and turnover, has been overlooked, in particular, for treatment planning with radionuclide therapy. Gallium-67 could also allow non-PET facilities to participate in theranostic imaging prior to treatment or for monitoring response after therapy. Gallium-67 could play a niche role in the future development of personalised medicine with theranostics. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

27. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author

Amgad, Mohamed, Stovgaard, Elisabeth Specht, Balslev, Eva, Thagaard, Jeppe, Chen, Weijie, Dudgeon, Sarah, Sharma, Ashish, Kerner, Jennifer K., Denkert, Carsten, Yuan, Yinyin, AbdulJabbar, Khalid, Wienert, Stephan, Savas, Peter, Voorwerk, Leonie, Beck, Andrew H., Madabhushi, Anant, Hartman, Johan, Sebastian, Manu M., Horlings, Hugo M., Hudeček, Jan, Ciompi, Francesco, Moore, David A., Singh, Rajendra, Roblin, Elvire, Balancin, Marcelo Luiz, Mathieu, Marie-Christine, Lennerz, Jochen K., Kirtani, Pawan, Chen, I-Chun, Braybrooke, Jeremy P., Pruneri, Giancarlo, Demaria, Sandra, Adams, Sylvia, Schnitt, Stuart J., Lakhani, Sunil R., Rojo, Federico, Comerma, Laura, Badve, Sunil S., Khojasteh, Mehrnoush, Symmans, W. Fraser, Sotiriou, Christos, Gonzalez-Ericsson, Paula, Pogue-Geile, Katherine L., Kim, Rim S., Rimm, David L., Viale, Giuseppe, Hewitt, Stephen M., Bartlett, John M. S., Penault-Llorca, Frédérique, Goel, Shom, Lien, Huang-Chun, Loibl, Sibylle, Kos, Zuzana, Loi, Sherene, Hanna, Matthew G., Michiels, Stefan, Kok, Marleen, Nielsen, Torsten O., Lazar, Alexander J., Bago-Horvath, Zsuzsanna, Kooreman, Loes F. S., Van Der Laak, Jeroen A. W. M., Saltz, Joel, Gallas, Brandon D., Kurkure, Uday, Barnes, Michael, Salgado, Roberto, Cooper, Lee A. D., Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Gown, Allen, Lo, Amy, Sapino, Anna, Moreira, Andre, Richardson, Andrea, Vingiani, Andrea, Bellizzi, Andrew M., Tutt, Andrew, Guerrero-Zotano, Angel, Grigoriadis, Anita, Ehinger, Anna, Garrido-Castro, Anna C., Vincent-Salomon, Anne, Laenkholm, Anne-Vibeke, Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Castaneda, Carlos, Ballesteroes-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Swanton, Charles, Solinas, Cinzia, Hiley, Crispin, Drubay, Damien, Bethmann, Daniel, Dillon, Deborah A., Larsimont, Denis, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Brogi, Edi, Perez, Edith, ElGabry, Ehab A., Blackley, Elizabeth F., Reisenbichler, Emily, Bellolio, Enrique, Chmielik, Ewa, Gaire, Fabien, Andre, Fabrice, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Gruosso, Forbius Tina, Peale, Franklin, Hirsch, Fred R., Klaushen, Frederick, Acosta-Haab, Gabriela, Farshid, Gelareh, Van Den Eynden, Gert, Curigliano, Giuseppe, Floris, Giuseppe, Broeckx, Glenn, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Cree, Ian, Nederlof, Iris, Frahm, Isabel, Brcic, Iva, Chan, Jack, Hall, Jacqueline A., Ziai, James, Brock, Jane, Wesseling, Jelle, Giltnane, Jennifer, Lemonnier, Jerome, Zha, Jiping, M. Ribeiro, Joana, Carter, Jodi M., Hainfellner, Johannes, Quesne, John Le, Juco, Jonathan W., Reis-Filho, Jorge, Van Den Berg, Jose, Sanchez, Joselyn, Sparano, Joseph, Cucherousset, Joël, Araya, Juan Carlos, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Willard-Gallo, Karen, Sikorska, Karolina, Weber, Karsten, Steele, Keith E., Emancipator, Kenneth, El Bairi, Khalid, Blenman, Kim R. M., Allison, Kimberly H., Van De Vijver, Koen K., Korski, Konstanty, Pusztai, Lajos, Buisseret, Laurence, Shi, Leming, Shi-Wei, Liu, Molinero, Luciana, Estrada, M. Valeria, Van Seijen, Maartje, Lacroix-Triki, Magali, Cheang, Maggie C. U., Bakir, Maise Al, Van De Vijver, Marc, Dieci, Maria Vittoria, Rebelatto, Marlon C., Piccart, Martine, Goetz, Matthew P., Preusser, Matthias, Sanders, Melinda E., Regan, Meredith M., Christie, Michael, Misialek, Michael, Ignatiadis, Michail, De Maaker, Michiel, Van Bockstal, Mieke, Castillo, Miluska, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Jelinic, Petar, Watson, Peter H., Francis, Prudence A., Russell, Prudence A., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, De Wind, Roland, Shui, Ruohong, Declercq, Sabine, Leung, Sam, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Willis, Scooter, Ely, Scott, Kim, Seong- Rim, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shi-Wei, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Fox, Stephen B., Luen, Stephen J., Naber, Stephen, Luz, Sua, Fineberg, Susan, Soler, Teresa, Gevaert, Thomas, D’Alfons, Timothy, John, Tom, Sugie, Tomohagu, Bossuyt, Veerle, Manem, Venkata, Cámaea, Vincente Peg, Tong, Weida, Yang, Wentao, Tran, William T., Wang, Yihong, Allory, Yves, and Husain, Zaheed

Subjects
631/67/580, 692/4028/67/1857, 631/67/2321, 692/53/2422, review-article, Review Article, 631/67/1347, humanities, 3. Good health
Abstract

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI), Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University., Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance., Funder: The Canadian Cancer Society, Funder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194, Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

28. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Author

Kos, Zuzana, Roblin, Elvire, Kim, Rim S., Michiels, Stefan, Gallas, Brandon D., Chen, Weijie, Van De Vijver, Koen K., Goel, Shom, Adams, Sylvia, Demaria, Sandra, Viale, Giuseppe, Nielsen, Torsten O., Badve, Sunil S., Symmans, W. Fraser, Sotiriou, Christos, Rimm, David L., Hewitt, Stephen, Denkert, Carsten, Loibl, Sibylle, Luen, Stephen J., Bartlett, John M. S., Savas, Peter, Pruneri, Giancarlo, Dillon, Deborah A., Cheang, Maggie Chon U., Tutt, Andrew, Hall, Jacqueline A., Kok, Marleen, Horlings, Hugo M., Madabhushi, Anant, Van Der Laak, Jeroen, Ciompi, Francesco, Laenkholm, Anne-Vibeke, Bellolio, Enrique, Gruosso, Tina, Fox, Stephen B., Araya, Juan Carlos, Floris, Giuseppe, Hudeček, Jan, Voorwerk, Leonie, Beck, Andrew H., Kerner, Jen, Larsimont, Denis, Declercq, Sabine, Van Den Eynden, Gert, Pusztai, Lajos, Ehinger, Anna, Yang, Wentao, AbdulJabbar, Khalid, Yuan, Yinyin, Singh, Rajendra, Hiley, Crispin, Bakir, Maise Al, Lazar, Alexander J., Naber, Stephen, Wienert, Stephan, Castillo, Miluska, Curigliano, Giuseppe, Dieci, Maria-Vittoria, André, Fabrice, Swanton, Charles, Reis-Filho, Jorge, Sparano, Joseph, Balslev, Eva, Chen, I-Chun, Stovgaard, Elisabeth Ida Specht, Pogue-Geile, Katherine, Blenman, Kim R. M., Penault-Llorca, Frédérique, Schnitt, Stuart, Lakhani, Sunil R., Vincent-Salomon, Anne, Rojo, Federico, Braybrooke, Jeremy P., Hanna, Matthew G., Soler-Monsó, M. Teresa, Bethmann, Daniel, Castaneda, Carlos A., Willard-Gallo, Karen, Sharma, Ashish, Lien, Huang-Chun, Fineberg, Susan, Thagaard, Jeppe, Comerma, Laura, Gonzalez-Ericsson, Paula, Brogi, Edi, Loi, Sherene, Saltz, Joel, Klaushen, Frederick, Cooper, Lee, Amgad, Mohamed, Moore, David A., Salgado, Roberto, Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Gown, Allen, Lo, Amy, Sapino, Anna, Moreira, Andre M., Richardson, Andrea, Vingiani, Andrea, Bellizzi, Andrew M., Guerrero, Angel, Grigoriadis, Anita, Garrido-Castro, Ana C., Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Ballesteroes-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Solinas, Cinzia, Drubay, Damien, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Perez, Edith, ElGabry, Ehab A., Blackley, Elizabeth F., Reisenbichler, Emily, Chmielik, Ewa, Gaire, Fabien, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Peale, Franklin, Hirsch, Fred R., Acosta-Haab, Gabriela, Farshid, Gelareh, Broeckx, Glenn, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Cree, Ian, Nederlof, Iris, Frahm, Isabel, Brcic, Iva, Chan, Jack, Ziai, James, Brock, Jane, Weseling, Jelle, Giltnane, Jennifer, Lemonnier, Jerome, Zha, Jiping, Ribeiro, Joana, Lennerz, Jochen K., Carter, Jodi M., Hartman, Johan, Hainfellner, Johannes, Le Quesne, John, Juco, Jonathan W., Van Den Berg, Jose, Sanchez, Joselyn, Cucherousset, Joël, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Sikorska, Karolina, Weber, Karsten, Steele, Keith E., Emancipator, Kenneth, El Bairi, Khalid, Allison, Kimberly H., Korski, Konstanty, Buisseret, Laurence, Shi, Leming, Kooreman, Loes F. S., Molinero, Luciana, Estrada, M. Valeria, Van Seijen, Maartje, Lacroix-Triki, Magali, Sebastian, Manu M., Balancin, Marcelo L., Mathieu, Marie-Christine, Van De Vijver, Mark, Rebelatto, Marlon C., Piccart, Martine, Goetz, Matthew P., Preusser, Matthias, Khojasteh, Mehrnoush, Sanders, Melinda E., Regan, Meredith M., Barnes, Michael, Christie, Michael, Misialek, Michael, Ignatiadis, Michail, De Maaker, Michiel, Van Bockstal, Mieke, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Kirtani, Pawan, Watson, Peter H., Jelinic, Peter, Francis, Prudence A., Russell, Prudence A., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, De Wind, Roland, Shui, Ruohong, Leung, Samuel, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Dudgeon, Sarah, Willis, Scooter, Ely, Scott, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shiwei, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Luz, Sua, Gevaert, Thomas, D’Alfons, Timothy, John, Tom, Sugie, Tomohagu, Kurkure, Uday, Bossuyt, Veerle, Manem, Venkata, Cámaea, Vincente Peg, Tong, Weida, Tran, William T., Wang, Yihong, Allory, Yves, Husain, Zaheed, and Bago-Horvath, Zsuzsanna

Subjects
692/53/2422, article, 3. Good health, 631/67/580/1884
Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.

29. Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Author

Hudeček, Jan, Voorwerk, Leonie, Van Seijen, Maartje, Nederlof, Iris, De Maaker, Michiel, Van Den Berg, Jose, Van De Vijver, Koen K., Sikorska, Karolina, Adams, Sylvia, Demaria, Sandra, Viale, Giuseppe, Nielsen, Torsten O., Badve, Sunil S., Michiels, Stefan, Symmans, William Fraser, Sotiriou, Christos, Rimm, David L., Hewitt, Stephen M., Denkert, Carsten, Loibl, Sibylle, Loi, Sherene, Bartlett, John M. S., Pruneri, Giancarlo, Dillon, Deborah A., Cheang, Maggie C. U., Tutt, Andrew, Hall, Jacqueline A., Kos, Zuzana, Salgado, Roberto, Kok, Marleen, Horlings, Hugo M., Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Lazar, Alexander J., Gown, Allen, Lo, Amy, Sapino, Anna, Madabhushi, Anant, Moreira, Andre, Richardson, Andrea, Vingiani, Andrea, Beck, Andrew H., Bellizzi, Andrew M., Guerrero, Angel, Grigoriadis, Anita, Ehinger, Anna, Garrido-Castro, Ana, Vincent-Salomon, Anne, Laenkholm, Anne-Vibeke, Sharma, Ashish, Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Gallas, Brandon D., Castaneda, Carlos, Ballesteros-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Swanton, Charles, Solinas, Cinzia, Hiley, Crispin, Drubay, Damien, Bethmann, Daniel, Moore, David A., Larsimont, Denis, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Brogi, Edi, Perez, Edith, ElGabry, Ehab A., Stovgaard, Elisabeth Specht, Blackley, Elizabeth F., Roblin, Elvire, Reisenbichler, Emily, Bellolio, Enrique, Balslev, Eva, Chmielik, Ewa, Gaire, Fabien, Andre, Fabrice, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Rojo, Federico, Gruosso, Tina, Ciompi, Francesco, Peale, Franklin, Hirsch, Fred R., Klauschen, Frederick, Penault-Llorca, Frédérique, Acosta Haab, Gabriela, Farshid, Gelareh, Van Den Eynden, Gert, Curigliano, Giuseppe, Floris, Giuseppe, Broeckx, Glenn, Gonzalez-Ericsson, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Lien, Huang-Chun, Chen, I-Chun, Cree, Ian, Frahm, Isabel, Brcic, Iva, Chan, Jack, Ziai, James, Brock, Jane, Wesseling, Jelle, Giltnane, Jennifer, Kerner, Jennifer K., Thagaard, Jeppe, Braybrooke, Jeremy P., Van Der Laak, Jeroen A. W. M., Lemonnier, Jerome, Zha, Jiping, Ribeiro, Joana, Lennerz, Jochen K., Carter, Jodi M., Saltz, Joel, Hartman, Johan, Hainfellner, Johannes, Quesne, John Le, Juco, Jonathon W., Reis-Filho, Jorge, Sanchez, Joselyn, Sparano, Joseph, Cucherousset, Joël, Araya, Juan Carlos, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Willard-Gallo, Karen, Weber, Karsten, Pogue-Geile, Katherine L., Steele, Keith E., Emancipator, Kenneth, AbdulJabbar, Khalid, El Bairi, Khalid, Blenman, Kim R. M., Allison, Kimberly H., Korski, Konstanty, Pusztai, Lajos, Comerma, Laura, Buisseret, Laurence, Cooper, Lee A. D., Shi, Leming, Kooreman, Loes F. S., Molinero, Luciana, Estrada, M. Valeria, Lacroix-Triki, Magali, Al Bakir, Maise, Sebastian, Manu M., Van De Vijver, Marc, Balancin, Marcelo Luiz, Dieci, Maria Vittoria, Mathieu, Marie-Christine, Rebelatto, Marlon C., Piccart, Martine, Hanna, Matthew G., Goetz, Matthew P., Preusser, Matthias, Khojasteh, Mehrnoush, Sanders, Melinda E., Regan, Meredith M., Barnes, Michael, Christie, Michael, Misialek, Michael, Ignatiadis, Michail, Van Bockstal, Mieke, Castillo, Miluska, Amgad, Mohamed, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Gonzalez-Ericsson, Paula, Kirtani, Pawan, Jelinic, Petar, Watson, Peter H., Savas, Peter, Francis, Prudence A., Russell, Prudence A., Singh, Rajendra, Kim, Rim S., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, De Wind, Roland, Shui, Ruohong, De Clercq, Sabine, Leung, Sam, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Dudgeon, Sarah, Willis, Scooter, Ely, Scott, Kim, Seong-Rim, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shi-Wei, Goel, Shom, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Wienert, Stephan, Fox, Stephen B., Luen, Stephen J., Naber, Stephen, Schnitt, Stuart J., Sua, Luz F., Lakhani, Sunil R., Fineberg, Susan, Soler, Teresa, Gevaert, Thomas, D’Alfonso, Timothy, John, Tom, Sugie, Tomohagu, Kurkure, Uday, Bossuyt, Veerle, Manem, Venkata, Cámara, Vincente Peg, Tong, Weida, Chen, Weijie, Yang, Wentao, Tran, William T., Wang, Yihong, Yuan, Yinyin, Allory, Yves, Husain, Zaheed, and Bago-Horvath, Zsuzsanna

Subjects
692/53, review-article, Review Article, 631/67/1347, 692/4028/67/580, 631/67/1857, 3. Good health
Abstract

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006, Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.

30. Safety and tolerability of Miltuximab ® - a first in human study in patients with advanced solid cancers.

Author

Sabanathan D, Campbell DH, Velonas VM, Wissmueller S, Mazure H, Trifunovic M, Poursoltan P, Ho Shon K, Mackay TR, Lund ME, Lu Y, Roach PJ, Bailey DL, Walsh BJ, Gillatt D, and Gurney H

Abstract

Objectives: Miltuximab ® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab ® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab ® radiolabelled with Gallium-67 ([ 67 Ga]Ga-DOTA-Miltuximab ® ). The primary study endpoint was to establish safety and tolerability of Miltuximab ® . Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis., Methods: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [ 67 Ga]Ga-DOTA-Miltuximab ® . Cohort 1 received [ 67 Ga]Ga-DOTA-Miltuximab ® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab ® -DOTA 1 hour prior to [ 67 Ga]Ga-DOTA-Miltuximab ® . Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans., Results: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [ 67 Ga]Ga-DOTA-Miltuximab ® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab ® -DOTA. Dosimetry analysis showed a favorable exposure profile. [ 67 Ga]Ga-DOTA-Miltuximab ® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life., Conclusions: This study is the first in human for Miltuximab ® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab ® as a theranostic agent in a planned Phase I human trial., (© 2021 mums.ac.ir All rights reserved.)

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results