1,022 results on '"Abou-Alfa, Ghassan K"'
Search Results
2. Pharmacokinetics/pharmacodynamics of ivosidenib in advanced IDH1-mutant cholangiocarcinoma: findings from the phase III ClarIDHy study
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Fan, Bin, Abou-Alfa, Ghassan K., Zhu, Andrew X., Pandya, Shuchi S., Jia, Hongxia, Yin, Feng, Gliser, Camelia, Hua, Zhaowei, Hossain, Mohammad, and Yang, Hua
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- 2024
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3. ASO Visual Abstract: Has Management of Intrahepatic Cholangiocarcinoma Evolved with the Evidence? Trends and Practice Patterns from the National Cancer Database
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Schleimer, Lauren E., Kalvin, Hannah L., Ellis, Ryan J., Kingham, T. Peter, Soares, Kevin C., D’Angelica, Michael I., Balachandran, Vinod P., Drebin, Jeffrey, Cercek, Andrea, Abou-Alfa, Ghassan K., O’Reilly, Eileen M., Harding, James J., Gönen, Mithat, Wei, Alice C., and Jarnagin, William R.
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- 2024
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4. Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data.
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Zack, Travis, Losert, Kurt P, Maisel, Samantha M, Wild, Jennifer, Yaqubie, Amin, Herman, Michael, Knox, Jennifer J, Mayer, Robert J, Venook, Alan P, Butte, Atul, O'Neill, Allison F, Abou-Alfa, Ghassan K, and Gordan, John D
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Liver Disease ,Cancer ,Rare Diseases ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology - Abstract
The incidence and biochemical consequences of rare tumor subtypes are often hard to study. Fibrolamellar liver cancer (FLC) is a rare malignancy affecting adolescents and young adults. To better characterize the incidence and biochemical consequences of this disease, we combined a comprehensive analysis of the electronic medical record and national payer data and found that FLC incidence is likely five to eight times higher than previous estimates. By employing unsupervised learning on clinical laboratory data from patients with hyperammonemia, we find that FLC-associated hyperammonemia mirrors metabolic dysregulation in urea cycle disorders. Our findings demonstrate that advanced computational analysis of rich clinical datasets can provide key clinical and biochemical insights into rare cancers.
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- 2023
5. Exposure-Response Analyses of Tremelimumab Monotherapy or in Combination with Durvalumab in Patients with Unresectable Hepatocellular Carcinoma
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Song, Xuyang, Kelley, Robin Kate, Khan, Anis A, Standifer, Nathan, Zhou, Diansong, Lim, KyoungSoo, Krishna, Rajesh, Liu, Lu, Wang, Kun, McCoon, Patricia, Negro, Alejandra, He, Philip, Gibbs, Megan, Kurland, John F, and Abou-Alfa, Ghassan K
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Rare Diseases ,Clinical Research ,Cancer ,Humans ,Carcinoma ,Hepatocellular ,Treatment Outcome ,Antineoplastic Combined Chemotherapy Protocols ,Liver Neoplasms ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeA novel single-dose regimen of 300 mg tremelimumab in combination with durvalumab [Single Tremelimumab Regular Interval Durvalumab (STRIDE)] has demonstrated a favorable benefit-risk profile in the phase I/II Study 22 (NCT02519348) and phase III HIMALAYA study (NCT03298451). This study evaluated the pharmacokinetics, exposure-response, and exposure-pharmacodynamics relationships of tremelimumab in patients with unresectable hepatocellular carcinoma (uHCC).Patients and methodsA previous tremelimumab population pharmacokinetic model was validated using data from parts 2 and 3 of Study 22. Exposure-response analyses explored relationships of tremelimumab exposure with efficacy and safety. Pharmacokinetics and pharmacodynamics relationships were evaluated using linear and nonlinear regression models.ResultsThe observed pharmacokinetics of tremelimumab in uHCC were consistent with predictions; no significant covariates were identified. Tremelimumab exposure was not significantly associated with adverse events, objective response rate, or progression-free survival. Overall survival (OS) was longer for patients with tremelimumab exposure, minimum serum drug concentration (Cmin1) ≥ median versus Cmin1 < median (18.99 months vs. 10.97 months), but this exposure-survival analysis might be confounded with baseline characteristics of albumin level and neutrophil to lymphocyte ratio, which had a significant impact on OS (P = 0.0004 and 0.0001, respectively). The predicted Cmin1 of tremelimumab in STRIDE regimen (12.9 μg/mL) was greater than the estimated concentration of tremelimumab eliciting half-maximal increases (EC50 = 5.24 μg/mL) in CD8+Ki67+ T-cell counts.ConclusionsOur findings support novel insights into tremelimumab pharmacokinetics and exposure-response relationships in HCC and support the clinical utility of the STRIDE regimen in patients with uHCC.
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- 2023
6. A multi‐analyte cell‐free DNA–based blood test for early detection of hepatocellular carcinoma
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Lin, Nan, Lin, Yongping, Xu, Jianfeng, Liu, Dan, Li, Diange, Meng, Hongyu, Gallant, Maxime A, Kubota, Naoto, Roy, Dhruvajyoti, Li, Jason S, Gorospe, Emmanuel C, Sherman, Morris, Gish, Robert G, Abou‐Alfa, Ghassan K, Nguyen, Mindie H, Taggart, David J, Van Etten, Richard A, Hoshida, Yujin, and Li, Wei
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Rare Diseases ,Cancer ,Genetics ,Prevention ,Clinical Research ,Liver Disease ,Liver Cancer ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Good Health and Well Being ,Carcinoma ,Hepatocellular ,Cell-Free Nucleic Acids ,Early Detection of Cancer ,Hematologic Tests ,Humans ,Liver Neoplasms ,Prospective Studies ,alpha-Fetoproteins ,Clinical sciences - Abstract
The limited performance of guideline-recommended abdominal ultrasound and serum alpha-fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers for more accurate detection of early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate the performance of the HelioLiver Test, a multi-analyte blood test combining cell-free DNA methylation patterns, clinical variables, and protein tumor markers. A blinded, multicenter validation study was performed with 247 subjects, including 122 subjects with HCC and 125 control subjects with chronic liver disease. The performance of the HelioLiver Test was compared with AFP and the GALAD score as established HCC surveillance blood tests. The performance of the HelioLiver Test (area under the receiver operating characteristic curve [AUROC] = 0.944) was superior to both AFP (AUROC = 0.851; p < 0.0001) and GALAD (AUROC = 0.899; p < 0.0001). Using a prespecified diagnostic algorithm, the HelioLiver Test showed sensitivities of 85% (95% confidence interval [CI], 78%-90%) for HCC of any stage and 76% (95% CI, 60%-87%) for early stage (American Joint Committee on Cancer [AJCC] I and II) HCC. In contrast, AFP (≥20 ng/mL) alone and the GALAD score (≥-0.63) showed lower sensitivities of 62% (95% CI, 54%-70%) and 75% (95% CI, 67%-82%) for HCC overall, and 57% (95% CI, 40%-71%) and 65% (95% CI, 49%-79%) for early stage (AJCC I and II) HCC, respectively. The specificities of the HelioLiver Test (91%; 95% CI, 85%-95%), AFP (97%; 95% CI, 92%-99%), and the GALAD score (94%; 95% CI, 88%-97%) were similar for control subjects. The HelioLiver Test showed superior performance for HCC detection compared to with both AFP and the GALAD score and warrants further evaluation in HCC surveillance settings.
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- 2022
7. Factors affecting outcomes of Yttrium-90 radioembolization in heavily pretreated patients with intrahepatic cholangiocarcinoma
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Zhao, Ken, Erinjeri, Joseph P., Sotirchos, Vlasios S., Alexander, Erica S., Moussa, Amgad M., Marinelli, Brett, Ziv, Etay, Sofocleous, Constantinos T., Abou-Alfa, Ghassan K., Jarnagin, William R., Karimi, Anita, and Yarmohammadi, Hooman
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- 2023
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8. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
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Azevedo, Sergio, Braghiroli, Maria Ignez, Girotto, Gustavo, Bragagnoli, Arinilda, Branco, Ricardo, Faccio, Adilson, Moretto, Andrea, Skare, Nils, Dutra, Jamille, Viola, Luciana, Vianna, Karina, Meton, Fernando, Sette, Claudia, Faulhaber, Amanda, Tam, Vincent C., Couture, Felix, Biagi, Jim, Castel, Helene, Mulder, Karen, Ko, Yoo-Joung, Zbuk, Kevin, Welch, Stephen, Beaudoin, Annie, Heurgué, Alexandra, Assenat, Eric, Archambeaud, Isabelle, Tougeron, David, Peron, Jean-Marie, Gilabert, Marine, Bronowicki, Jean-Pierre, Cattan, Stephane, Blanc, Jean-Frederic, Bouattour, Mohamed, Phelip, Jean-Marc, Boige, Valerie, Michel, Pierre, Frin, Anne-Claire, De Toni, Enrico N., Berres, Marie-Luise, Vogel, Arndt, Berg, Thomas, Ettrich, Thomas, Waldschmidt, Dirk, Wedemeyer, Hans Heinrich, Worns, Marcus-Alexander, Bitzer, Michael, Weiss, Karl-Heinz, Lau, George, Chan, Stephen L., Yau, Thomas, Tai, Yin Ping, Lee, Ann Shing, Thungappa, Satheesh Chiradoni, N, Lokesh K., Sureshchand Ostwal, Vikas, Ashok, Kattimani Kiran, Mittal, Sushant, Goyal, Hari, Srinivasan, Sankar, Biswas, Ghanashyam, Mohan, Mallavarapu, Limaye, Sewanti, Asarawala, Nirav, Rimassa, Lorenza, Falcone, Alfredo, Gianni, Luca, Gasbarrini, Antonio, Daniele, Bruno, Avallone, Antonio, Paolo Frassineti, Giovanni Luca, Roila, Fausto, Kudo, Masatoshi, Kawaoka, Tomokazu, Morimoto, Manabu, Takikawa, Yasuhiro, Kato, Naoya, Yamashita, Tatsuya, Osaki, Yukio, Motomura, Kenta, Tateishi, Ryosuke, Ohkawa, Kazuyoshi, Wada, Yoshiyuki, Onishi, Hideki, Sasahira, Naoki, Inaba, Yoshitaka, Kurosaki, Masayuki, Tsuji, Kunihiko, Takei, Yoshiyuki, Aramaki, Takeshi, Hagihara, Atsushi, Furuse, Junji, Kioka, Kiyohide, Koga, Hironori, Sasaki, Yutaka, Numata, Kazushi, Tada, Toshifumi, Kawaguchi, Yasunori, Nadano, Seijin, Vasilyev, Alexander, Breder, Valery, Lipatov, Oleg, Dvorkin, Mikhail, Zarubenkov, Oleg, Kutukova, Svetlana, Ponomarev, Roman, Shostka, Kirill, Alyasova, Anna, Topuzov, Eldar, Severtsev, Alexey, Petrov, Yuryi, Erygin, Dmitriy, Berdov, Boris, Kang, Yoon-Koo, Tak, Won-Young, Park, Joong-Won, Lim, Ho Yeong, Heo, Jeong, Kim, Jee Hyun, Kim, Tae-You, Choi, Hye Jin, Varela, María, Reig Monzon, María Elisa, Sangro, Bruno, Martin, Carlos Gómez, Ponce, Carmen Guillén, López, Carlos, Cheng, Ann-Lii, Chao, Yee, Feng, Yin-Hsun, Jeng, Long-Bin, Hung, Chao-Hung, Hou, Ming-Mo, Wang Tsang-En Wang, Jing-Houng, Yen, Chia-Jui, Sukeepaisarnjaroen, Wattana, Sunpaweravong, Patrapim, Charoentum, Chaiyut, Tanasanvimon, Suebpong, Sirachainan, Ekaphop, Ungtrakul, Teerapat, Prasongsook, Naiyarat, Maneenil, Kunlatida, Jitpewngarm, Wittawat, Ostapenko, Yurii, Skoryi, Denys, Bondarenko, Igor, Shparyk, Yaroslav, Trukhin, Dmytro, Hotko, Yevhen, Ursol, Grygorii, Kryzhanivska, Anna, Abou-Alfa, Ghassan K., Mody, Kabir, Dayyani, Farshid, Al-Rajabi, Raed, Yarchoan, Mark, Gandhi, Sunil, Crysler, Oxana, He, Aiwu Ruth, Reeves, James, Bahary, Nathan, Mahipal, Amit, Kelley, Robin Kate, Dasgupta, Anirudha, Rowe, Julie, Thota, Ramya, Beg, Muhammad, Morse, Michael, Choi, Sung-hee, Crocenzi, Todd, Somer, Bradley, Abrams, Thomas, Denlinger, Crystal, Zhang, Yue, Sharma, Nisha, Dao, Tu V., Thinh, Nguyen Tien, Tuyet Phuong, Le Thi, Sangro, B., Chan, S.L., Kelley, R.K., Lau, G., Kudo, M., Sukeepaisarnjaroen, W., Yarchoan, M., De Toni, E.N., Furuse, J., Kang, Y.K., Galle, P.R., Rimassa, L., Heurgué, A., Tam, V.C., Van Dao, T., Thungappa, S.C., Breder, V., Ostapenko, Y., Reig, M., Makowsky, M., Paskow, M.J., Gupta, C., Kurland, J.F., Negro, A., and Abou-Alfa, G.K.
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- 2024
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9. Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers
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Harding, James J., Piha-Paul, Sarina A., Shah, Ronak H., Murphy, Jessica J., Cleary, James M., Shapiro, Geoffrey I., Quinn, David I., Braña, Irene, Moreno, Victor, Borad, Mitesh, Loi, Sherene, Spanggaard, Iben, Park, Haeseong, Ford, James M., Arnedos, Mónica, Stemmer, Salomon M., de la Fouchardiere, Christelle, Fountzilas, Christos, Zhang, Jie, DiPrimeo, Daniel, Savin, Casey, Duygu Selcuklu, S., Berger, Michael F., Eli, Lisa D., Meric-Bernstam, Funda, Jhaveri, Komal, Solit, David B., and Abou-Alfa, Ghassan K.
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- 2023
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10. Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade
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Kelley, Robin Kate, Miksad, Rebecca, Cicin, Irfan, Chen, YenHsun, Klümpen, Heinz-Josef, Kim, Stefano, Lin, Zhong-Zhe, Youkstetter, Jillian, Hazra, Saswati, Sen, Suvajit, Cheng, Ann-Lii, El-Khoueiry, Anthony B, Meyer, Tim, and Abou-Alfa, Ghassan K
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Cancer ,Digestive Diseases ,Liver Cancer ,Clinical Trials and Supportive Activities ,Liver Disease ,Rare Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Administration ,Oral ,Adult ,Aged ,Aged ,80 and over ,Anilides ,Bilirubin ,Carcinoma ,Hepatocellular ,Female ,Humans ,Liver Function Tests ,Liver Neoplasms ,Male ,Middle Aged ,Pyridines ,Retrospective Studies ,Serum Albumin ,Survival Analysis ,Treatment Outcome ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundAlbumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC.MethodsPatients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as ≤ -2.60 score and a grade of 2 as a score of > -2.60 to ≤ -1.39.ResultsCabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio [HR] [95% CI]: 0.63 [0.46-0.86] and 0.42 [0.32-0.56]) and ALBI grade 2 (HR [95% CI]: 0.84 [0.66-1.06] and 0.46 [0.37-0.58]) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup.DiscussionThese results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2.Trial registration numberClinicalTrials.gov number, NCT01908426.
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- 2022
11. Immune Strategies for Gastrointestinal Cancer: HCC
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Khalil, Danny N., El Dika, Imane, Azhari, Hassan, Harding, James J., O’Reilly, Eileen M., Abou-Alfa, Ghassan K., Theobald, Matthias, Series Editor, Moehler, Markus, editor, and Foerster, Friedrich, editor
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- 2023
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12. Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers
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Yarchoan, Mark, Cope, Leslie, Ruggieri, Amanda N, Anders, Robert A, Noonan, Anne M, Goff, Laura W, Goyal, Lipika, Lacy, Jill, Li, Daneng, Patel, Anuj K, He, Aiwu R, Abou-Alfa, Ghassan K, Spencer, Kristen, Kim, Edward J, Davis, S Lindsey, McRee, Autumn J, Kunk, Paul R, Goyal, Subir, Liu, Yuan, Dennison, Lauren, Xavier, Stephanie, Mohan, Aditya A, Zhu, Qingfeng, Wang-Gillam, Andrea, Poklepovic, Andrew, Chen, Helen X, Sharon, Elad, Lesinski, Gregory B, and Azad, Nilofer S
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Clinical Trials and Supportive Activities ,Digestive Diseases ,Cancer ,Rare Diseases ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Aged ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Combined Chemotherapy Protocols ,Azetidines ,Biliary Tract Neoplasms ,Disease-Free Survival ,Female ,Humans ,Male ,Middle Aged ,Piperidines ,Progression-Free Survival ,Cancer immunotherapy ,Immunology ,Liver cancer ,Oncology ,Medical and Health Sciences - Abstract
BACKGROUNDMEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition.METHODSThis open-label phase II study randomized patients with BTC to atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1. The primary endpoint was progression-free survival (PFS).RESULTSSeventy-seven patients were randomized and received study therapy. The trial met its primary endpoint, with a median PFS of 3.65 months in the combination arm versus 1.87 months in the monotherapy arm (HR 0.58, 90% CI 0.35-0.93, 1-tail P = 0.027). One patient in the combination arm (3.3%) and 1 patient in the monotherapy arm (2.8%) had a partial response. Combination therapy was associated with more rash, gastrointestinal events, CPK elevations, and thrombocytopenia. Exploratory analysis of tumor biopsies revealed enhanced expression of antigen processing and presentation genes and an increase in CD8/FoxP3 ratios with combination treatment. Patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells had evidence of greater clinical benefit from the combination.CONCLUSIONThe combination of atezolizumab plus cobimetinib prolonged PFS as compared with atezolizumab monotherapy, but the low response rate in both arms highlights the immune-resistant nature of BTCs.TRIAL REGISTRATIONClinicalTrials.gov NCT03201458.FUNDINGNational Cancer Institute (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN); F. Hoffmann-La Roche, Ltd.; NCI, NIH (R01 CA228414-01 and UM1CA186691); NCI's Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancers (P50 CA062924); NIH Center Core Grant (P30 CA006973); and the Passano Foundation.
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- 2021
13. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study
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Kelley, Robin Kate, Sangro, Bruno, Harris, William, Ikeda, Masafumi, Okusaka, Takuji, Kang, Yoon-Koo, Qin, Shukui, Tai, David W-M, Lim, Ho Yeong, Yau, Thomas, Yong, Wei-Peng, Cheng, Ann-Lii, Gasbarrini, Antonio, Damian, Silvia, Bruix, Jordi, Borad, Mitesh, Bendell, Johanna, Kim, Tae-You, Standifer, Nathan, He, Philip, Makowsky, Mallory, Negro, Alejandra, Kudo, Masatoshi, and Abou-Alfa, Ghassan K
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,HIV/AIDS ,Orphan Drug ,Rare Diseases ,Cancer ,Biotechnology ,Clinical Research ,Digestive Diseases ,Clinical Trials and Supportive Activities ,Liver Cancer ,Patient Safety ,Liver Disease ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,6.2 Cellular and gene therapies ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Humanized ,Carcinoma ,Hepatocellular ,Female ,Humans ,Liver Neoplasms ,Male ,Middle Aged ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeThis phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348).Patients and methodsPatients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks). Safety was the primary end point. Secondary end points included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors v1.1 and overall survival; exploratory end points included circulating lymphocyte profiles.ResultsA total of 332 patients were enrolled (T300 + D, n = 75; durvalumab, n = 104; tremelimumab, n = 69; and T75 + D, n = 84). Tolerability was acceptable across arms, with grade ≥ 3 treatment-related adverse events occurring in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. Confirmed ORRs (95% CI) were 24.0% (14.9 to 35.3), 10.6% (5.4 to 18.1), 7.2% (2.4 to 16.1), and 9.5% (4.2 to 17.9), respectively. An early expansion of CD8+ lymphocytes was associated with response across arms, with highest proliferating CD8+ lymphocyte levels occurring in the T300 + D arm. The median (95% CI) overall survival was 18.7 (10.8 to 27.3), 13.6 (8.7 to 17.6), 15.1 (11.3 to 20.5), and 11.3 (8.4 to 15.0) months in the T300 + D, durvalumab, tremelimumab, and T75 + D arms, respectively.ConclusionAll regimens were found to be tolerable and clinically active; however, the T300 + D regimen demonstrated the most encouraging benefit-risk profile. The unique pharmacodynamic activity and association with ORR of the T300 + D regimen further support its continued evaluation in HCC.
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- 2021
14. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma
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Greten, Tim F, Abou-Alfa, Ghassan K, Cheng, Ann-Lii, Duffy, Austin G, El-Khoueiry, Anthony B, Finn, Richard S, Galle, Peter R, Goyal, Lipika, He, Aiwu Ruth, Kaseb, Ahmed O, Kelley, Robin Kate, Lencioni, Riccardo, Lujambio, Amaia, Hrones, Donna Mabry, Pinato, David J, Sangro, Bruno, Troisi, Roberto I, Woods, Andrea Wilson, Yau, Thomas, Zhu, Andrew X, and Melero, Ignacio
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Clinical Trials and Supportive Activities ,Liver Cancer ,Digestive Diseases ,Rare Diseases ,Vaccine Related ,Cancer ,Clinical Research ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Patient Safety ,Immunization ,Good Health and Well Being ,Carcinoma ,Hepatocellular ,Guidelines as Topic ,Humans ,Immunotherapy ,Liver Neoplasms ,antineoplastic protocols ,immunotherapy ,guidelines as topic ,liver neoplasms ,Oncology and carcinogenesis - Abstract
Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.
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- 2021
15. First-in-Human Study of INCB062079, a Fibroblast Growth Factor Receptor 4 Inhibitor, in Patients with Advanced Solid Tumors
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Harding, James J., Jungels, Christiane, Machiels, Jean-Pascal, Smith, David C., Walker, Chris, Ji, Tao, Jiang, Ping, Li, Xin, Asatiani, Ekaterine, Van Cutsem, Eric, and Abou-Alfa, Ghassan K.
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- 2023
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16. Phase 1b study of galunisertib and ramucirumab in patients with advanced hepatocellular carcinoma
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Harding, James J, K., Richard, Yaqubie, Amin, Cleverly, Ann, Zhao, Yumin, Gueorguieva, Ivelina, Lahn, Michael, Benhadji, Karim A, Kelley, Robin K, and Abou‐Alfa, Ghassan K
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Clinical Research ,Digestive Diseases ,Liver Disease ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Carcinoma ,Hepatocellular ,Female ,Humans ,Liver Neoplasms ,Male ,Maximum Tolerated Dose ,Middle Aged ,Nausea ,Prospective Studies ,Pyrazoles ,Quinolines ,Receptor ,Transforming Growth Factor-beta Type I ,Response Evaluation Criteria in Solid Tumors ,Vascular Endothelial Growth Factor A ,Vascular Endothelial Growth Factor Receptor-2 ,Vomiting ,alpha-Fetoproteins ,galunisertib ,HCC ,hepatocellular carcinoma ,Phase 1 ,ramucirumab ,TGF‐ ,β ,VEGF ,TGF-β ,Biochemistry and Cell Biology ,Oncology and carcinogenesis - Abstract
BackgroundPreclinical data suggest that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β signaling interact to stimulate angiogenesis and suppress antitumor immune responses. Thus, combined inhibition of both pathways may offer greater antitumor activity compared with VEGF-targeted antiangiogenic monotherapy against hepatocellular carcinoma (HCC).MethodsThis is a multicenter, open-label, phase 1b study of galunisertib, an inhibitor of TGF-β receptor 1, and ramucirumab, an anti-VEGF receptor 2 antibody, in patients with advanced HCC aiming to define the maximum tolerated dose (MTD). Secondary objectives included safety, pharmacokinetics (PK), antitumor efficacy, and plasma alpha-fetoprotein and TGF-β kinetics. Dose escalation employed a 3 + 3 design. Patients received galunisertib at 80 mg (cohort 1) or 150 mg (cohort 2) orally twice a day on days 1-14 of a 28-day cycle combined with ramucirumab 8 mg/kg intravenously every 2 weeks.ResultsEight patients were enrolled: three in cohort 1 and five in cohort 2 (two patients were unevaluable due to rapid disease progression and replaced). No dose-limiting toxicities were observed. Treatment-related adverse events (AEs) of any grade in ≥2 patients included nausea (25%) and vomiting (25%). There was one Grade 3 treatment-related AE, a cerebrovascular accident possibly related to ramucirumab. Galunisertib exposure was dose-proportional and not affected by ramucirumab. The RECIST version 1.1 objective response rate and disease control rate were 0% and 12.5%, respectively.ConclusionCombination therapy was safe and tolerable and displayed favorable PK. The MTD was established at galunisertib at 150 mg orally twice a day and ramucirumab 8 mg/kg intravenously every 2 weeks. The results do not support the preclinical hypothesis that blocking TGFβ signaling enhances efficacy of VEGF-targeted therapy; thus further clinical development was halted for the combination of galunisertib and ramucirumab.
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- 2021
17. Health diplomacy in action: The cancer legacy of the Good Friday Agreement
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Lawler, Mark, Sullivan, Richard, Abou-Alfa, Ghassan K., McCloskey, Karen, Keatley, Debbie, Feighan, Jennifer, Dahut, William, Mulroe, Eibhlin, Ladner, Robert, Genead, Mohamed, Lowery, Maeve, Gulley, James L., Scott, Christopher J., Longley, Daniel B., Culhane, Aedin, Gallagher, William M., Orr, Nick, Chanock, Stephen J., and Gopal, Satish
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- 2023
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18. Immune Strategies for Gastrointestinal Cancer: HCC
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Khalil, Danny N., primary, El Dika, Imane, additional, Azhari, Hassan, additional, Harding, James J., additional, O’Reilly, Eileen M., additional, and Abou-Alfa, Ghassan K., additional
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- 2023
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19. Phase Ib Study of Enzalutamide with or Without Sorafenib in Patients with Advanced Hepatocellular Carcinoma
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Harding, James J, Kelley, Robin K, Tan, Benjamin, Capanu, Marinela, Kinh, Gian, Shia, Jinru, Chou, Joanne F, Ferrer, Christine S, Boussayoud, Chayma, Muenkel, Kerri, Yarmohammadi, Hooman, Dika, Imane El, Khalil, Danny N, Ruiz, Carmen, Rodriguez‐Lee, Mariam, Kuhn, Peter, Wilton, John, Iyer, Renuka, and Abou‐Alfa, Ghassan K
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Liver Cancer ,Clinical Trials and Supportive Activities ,Rare Diseases ,Liver Disease ,Clinical Research ,Digestive Diseases ,Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Benzamides ,Carcinoma ,Hepatocellular ,Humans ,Liver Neoplasms ,Niacinamide ,Nitriles ,Phenylthiohydantoin ,Phenylurea Compounds ,Sorafenib ,Treatment Outcome ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Lessons learnedAndrogen receptor as assessed by immunohistochemistry is expressed in a high proportion of patients with hepatocellular carcinoma (HCC). Enzalutamide at 160 mg orally daily is safe and tolerable in patients with advanced HCC but has no single-agent antitumor activity. Enzalutamide, a CYP3A4 inducer, at a standard dose of 160 mg reduces the exposure of sorafenib, a CYP3A4 substrate. Enzalutamide and sorafenib is safe and tolerable in patients with advanced HCC, but the addition of enzalutamide to sorafenib did not enhance the antitumor activity of sorafenib.BackgroundAndrogen receptor (AR) interference is deleterious to hepatocellular carcinoma (HCC) in preclinical models.MethodsThis is a multicenter, phase Ib study of enzalutamide ± sorafenib in patients with advanced HCC. In part 1, a 3 + 3 dose de-escalation design with expansion established the recommended phase II dose (RP2D) of enzalutamide in patients in whom sorafenib treatment had failed. In part 2, a 3 + 3 dose escalation with expansion established the safety of enzalutamide with sorafenib in treatment-naive patients with HCC. Secondary objectives included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and determination of AR expression by immunohistochemistry. A 7-day run-in with sorafenib alone in part 2 allowed assessment of the impact of enzalutamide on sorafenib pharmacokinetics.ResultsIn part 1, 16 patients received enzalutamide 160 mg daily. No dose-limiting toxicity (DLT) occurred; 1 patient required dose reduction. Responses were not observed; median PFS and OS were 1.8 (95% confidence interval [CI]: 1.6-3.6) and 7 (95% CI: 3.6 to not reached [NR]) months, respectively. In part 2, patients received sorafenib 400 mg daily (4) or twice a day (8) both with enzalutamide at the recommended phase II dose-no DLTs were observed. ORR was 10% (95% CI: 0.3-44.5), and median PFS and OS were 2.9 (95% CI: 1.6 to NR) and 6.7 (95% CI: 4.6 to NR) months, respectively. Enzalutamide reduced sorafenib exposure by 60%. Tumor AR expression did not associate with outcome.ConclusionEnzalutamide is ineffective in HCC; further development is not supported by this study.
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- 2020
20. KDR genetic predictor of toxicities induced by sorafenib and regorafenib
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Quintanilha, Julia C. F., Geyer, Susan, Etheridge, Amy S., Racioppi, Alessandro, Hammond, Kelli, Crona, Daniel J., Peña, Carol E., Jacobson, Sawyer B., Marmorino, Federica, Rossini, Daniele, Cremolini, Chiara, Sanoff, Hanna K., Abou-Alfa, Ghassan K., and Innocenti, Federico
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- 2022
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21. Recurrence of Hepatocellular Carcinoma After Complete Radiologic Response to Trans-Arterial Embolization: A Retrospective Study on Patterns, Treatments, and Prognoses
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Ilagan, Crisanta H., Goldman, Debra A., Gönen, Mithat, Aveson, Victoria G., Babicky, Michelle, Balachandran, Vinod P., Drebin, Jeffrey A., Jarnagin, William R., Wei, Alice C., Kingham, T. Peter, Abou-Alfa, Ghassan K., Brown, Karen T., and D’Angelica, Michael I.
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- 2022
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22. Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma
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Kelley, Robin Kate, Meyer, Tim, Rimassa, Lorenza, Merle, Philippe, Park, Joong-Won, Yau, Thomas, Chan, Stephen L, Blanc, Jean-Frederic, Tam, Vincent C, Tran, Albert, Dadduzio, Vincenzo, Markby, David W, Kaldate, Rajesh, Cheng, Ann-Lii, El-Khoueiry, Anthony B, and Abou-Alfa, Ghassan K
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Cancer ,Clinical Trials and Supportive Activities ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Aged ,80 and over ,Anilides ,Carcinoma ,Hepatocellular ,Female ,Humans ,Liver Neoplasms ,Male ,Middle Aged ,Neoplasm Staging ,Placebos ,Prognosis ,Progression-Free Survival ,Protein Kinase Inhibitors ,Pyridines ,Reference Values ,Young Adult ,alpha-Fetoproteins ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeThe phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes.Patients and methodsSerum AFP was measured every 8 weeks by blinded, centralized testing. Outcomes were analyzed by baseline AFP bifurcated at 400 ng/mL and by on-treatment AFP response (≥20% decrease from baseline at Week 8). The optimal cutoff for change in AFP at Week 8 was evaluated using maximally selected rank statistics.ResultsMedian OS for cabozantinib versus placebo was 13.9 versus 10.3 months [HR, 0.81; 95% confidence interval (CI), 0.62-1.04] for patients with baseline AFP
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- 2020
23. Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial.
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Kelley, Robin Kate, Ryoo, Baek-Yeol, Merle, Philippe, Park, Joong-Won, Bolondi, Luigi, Chan, Stephen L, Lim, Ho Yeong, Baron, Ari D, Parnis, Francis, Knox, Jennifer, Cattan, Stéphane, Yau, Thomas, Lougheed, Julie C, Milwee, Steven, El-Khoueiry, Anthony B, Cheng, Ann-Lii, Meyer, Tim, and Abou-Alfa, Ghassan K
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Humans ,Carcinoma ,Hepatocellular ,Liver Neoplasms ,Anilides ,Pyridines ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Male ,Young Adult ,Sorafenib ,cabozantinib ,hepatocellular carcinoma ,sorafenib ,tyrosine kinase inhibitor ,Clinical Research ,Cancer ,Clinical Trials and Supportive Activities ,Digestive Diseases ,Rare Diseases ,Liver Cancer ,Liver Disease ,6.1 Pharmaceuticals - Abstract
ObjectiveIn the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy.MethodsCELESTIAL randomised (2:1) patients with advanced HCC and Child-Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo. Eligibility required prior treatment with sorafenib, and patients could have received ≤2 prior systemic regimens. The primary endpoint was OS. Outcomes in patients who had received sorafenib as the only prior therapy were analysed by duration of prior sorafenib (
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- 2020
24. Comparative Efficacy of Cabozantinib and Regorafenib for Advanced Hepatocellular Carcinoma
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Kelley, Robin K, Mollon, Patrick, Blanc, Jean-Frédéric, Daniele, Bruno, Yau, Thomas, Cheng, Ann-Lii, Valcheva, Velichka, Marteau, Florence, Guerra, Ines, and Abou-Alfa, Ghassan K
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Digestive Diseases ,Clinical Trials and Supportive Activities ,Liver Cancer ,Cancer ,Clinical Research ,Liver Disease ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Angiogenesis Inhibitors ,Anilides ,Antineoplastic Agents ,Carcinoma ,Hepatocellular ,Comparative Effectiveness Research ,Disease Progression ,Female ,Humans ,Liver Neoplasms ,Male ,Middle Aged ,Neoplasm Staging ,Outcome and Process Assessment ,Health Care ,Phenylurea Compounds ,Progression-Free Survival ,Pyridines ,Randomized Controlled Trials as Topic ,Sorafenib ,CELESTIAL ,Cabozantinib ,Hepatocellular carcinoma ,Indirect treatment comparison ,Matching-adjusted indirect comparison ,RESORCE ,Regorafenib ,Second-line ,Systemic therapy ,Targeted therapy ,Pharmacology and Pharmaceutical Sciences ,General Clinical Medicine ,Clinical sciences ,Pharmacology and pharmaceutical sciences - Abstract
BackgroundNo trials have compared cabozantinib and regorafenib for the second-line treatment of advanced hepatocellular carcinoma (HCC).ObjectivesConduct a matching-adjusted indirect comparison (MAIC) of the efficacy and safety of second-line cabozantinib and regorafenib in patients with advanced HCC and disease progression after prior sorafenib.MethodsThe CELESTIAL and RESORCE trials were used for indirect comparison of second-line cabozantinib and regorafenib in advanced HCC. Population-level data were available for RESORCE, individual patient data (IPD) for CELESTIAL. To align with RESORCE, the CELESTIAL population was limited to patients who received first-line sorafenib only. To minimize potential effect-modifying population differences, the CELESTIAL IPD were weighted to balance the distribution of clinically relevant baseline characteristics with those of RESORCE. Overall survival (OS) and progression-free survival (PFS) were evaluated for the matching-adjusted second-line CELESTIAL population and compared with those for RESORCE using weighted Kaplan-Meier curves and parametric modeling. Rates of grade 3/4 treatment-emergent adverse events (TEAEs) affecting > 5% of patients in any study arm were compared.ResultsIn the matching-adjusted second-line populations (CELESTIAL, effective sample size = 266; RESORCE, n = 573), median (95% confidence interval) OS was similar for cabozantinib and regorafenib (11.4 [8.9-17.0] versus 10.6 [9.1-12.1] months; p = 0.3474, log-rank test). Median PFS was longer for cabozantinib than regorafenib (5.6 [4.9-7.3] versus 3.1 [2.8-4.2] months; p = 0.0005, log-rank test). There was a trend for lower rates of some grade 3/4 TEAEs with regorafenib than with cabozantinib, which may reflect the exclusion of sorafenib-intolerant patients from RESORCE but not from CELESTIAL, a difference that the MAIC methods could not remove. Only diarrhea rates were statistically significantly lower for regorafenib (p ≤ 0.001).ConclusionsCabozantinib may achieve similar OS and prolonged PFS compared with regorafenib in patients with progressive advanced HCC after prior sorafenib.
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- 2020
25. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study
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Abou-Alfa, Ghassan K, Macarulla, Teresa, Javle, Milind M, Kelley, Robin K, Lubner, Sam J, Adeva, Jorge, Cleary, James M, Catenacci, Daniel V, Borad, Mitesh J, Bridgewater, John, Harris, William P, Murphy, Adrian G, Oh, Do-Youn, Whisenant, Jonathan, Lowery, Maeve A, Goyal, Lipika, Shroff, Rachna T, El-Khoueiry, Anthony B, Fan, Bin, Wu, Bin, Chamberlain, Christina X, Jiang, Liewen, Gliser, Camelia, Pandya, Shuchi S, Valle, Juan W, and Zhu, Andrew X
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Brain Disorders ,Clinical Trials and Supportive Activities ,Digestive Diseases ,Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Agents ,Bile Duct Neoplasms ,Cholangiocarcinoma ,Disease Progression ,Double-Blind Method ,Drug Resistance ,Neoplasm ,Enzyme Inhibitors ,Europe ,Female ,Glycine ,Humans ,Isocitrate Dehydrogenase ,Male ,Middle Aged ,Mutation ,Progression-Free Survival ,Pyridines ,Republic of Korea ,Time Factors ,United States ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundIsocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma.MethodsThis multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857.FindingsBetween Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8-10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6-4·2] vs 1·4 months [1·4-1·6]; hazard ratio 0·37; 95% CI 0·25-0·54; one-sided p
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- 2020
26. Second‐line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes
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Lowery, Maeve A, Goff, Laura W, Keenan, Bridget P, Jordan, Emmet, Wang, Rui, Bocobo, Andrea G, Chou, Joanne F, O’Reilly, Eileen M, Harding, James J, Kemeny, Nancy, Capanu, Marianela, Griffin, Ann C, McGuire, Joseph, Venook, Alan P, Abou‐Alfa, Ghassan K, and Kelley, Robin K
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Cancer ,Digestive Diseases ,Digestive Diseases - (Gallbladder) ,Liver Disease ,Clinical Trials and Supportive Activities ,Rare Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Biliary Tract Neoplasms ,Female ,Humans ,Kaplan-Meier Estimate ,Male ,Middle Aged ,Neoplasm Metastasis ,Neoplasm Staging ,Retreatment ,Retrospective Studies ,Treatment Failure ,Treatment Outcome ,Young Adult ,biliary cancer ,bile duct cancer ,chemotherapy ,cholangiocarcinoma ,gallbladder cancer ,second line ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Public health - Abstract
BackgroundAlthough gemcitabine plus platinum chemotherapy is the established first-line regimen for advanced biliary cancer (ABC), there is no standard second-line therapy. This study evaluated current practice and outcomes for second-line chemotherapy in patients with ABC across 3 US academic medical centers.MethodsInstitutional registries were reviewed to identify patients who had received second-line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes. Overall survival from the initiation of second-line chemotherapy (OS2) was estimated with Kaplan-Meier methods.ResultsThis study identified 198 patients with cholangiocarcinoma (intrahepatic [61.1%] or extrahepatic [14.1%]) or gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 was 11 months (95% confidence interval [CI], 8.8-13.1 months). The median OS2 for patients with intrahepatic cholangiocarcinoma was 13.4 months (95% CI, 10.7-17.8 months), which was longer than that for patients with extrahepatic cholangiocarcinoma (6.8 months; 95% CI, 5-10.6 months) or gallbladder carcinoma (9.4 months; 95% CI, 7.2-12.3 months; P = .018). The median time to second-line treatment failure was 2.2 months (95% CI, 1.8-2.7 months), and it was similar across tumor locations (P = .60).ConclusionsIn this large cohort of patients with ABC treated across 3 academic medical centers after the failure of first-line chemotherapy, the time to treatment failure on standard therapies was short, although the median OS2 was longer than has been reported previously, and more than half of the patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second-line chemotherapy for ABC and provides a contemporary benchmark for future clinical trials.
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- 2019
27. Rational development of combination therapies for biliary tract cancers
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Harding, James J., Khalil, Danny N., Fabris, Luca, and Abou-Alfa, Ghassan K.
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- 2023
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28. Effect of FGFR2 Alterations on Overall and Progression-Free Survival in Patients Receiving Systemic Therapy for Intrahepatic Cholangiocarcinoma
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Abou-Alfa, Ghassan K., Bibeau, Kristen, Schultz, Nikolaus, Yaqubie, Amin, Millang, Brittanie, Ren, Haobo, and Féliz, Luis
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- 2022
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29. Truncated FGFR2 is a clinically actionable oncogene in multiple cancers
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Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Kas, Sjors M., Rolfs, Frank, Lutz, Catrin, Lee, Jessica K., Klarenbeek, Sjoerd, Silverman, Ian M., Annunziato, Stefano, Chan, Chang S., Piersma, Sander R., Eijkman, Timo, Badoux, Madelon, Gogola, Ewa, Siteur, Bjørn, Sprengers, Justin, de Klein, Bim, de Goeij-de Haas, Richard R., Riedlinger, Gregory M., Ke, Hua, Madison, Russell, Drenth, Anne Paulien, van der Burg, Eline, Schut, Eva, Henneman, Linda, van Miltenburg, Martine H., Proost, Natalie, Zhen, Huiling, Wientjens, Ellen, de Bruijn, Roebi, de Ruiter, Julian R., Boon, Ute, de Korte-Grimmerink, Renske, van Gerwen, Bastiaan, Féliz, Luis, Abou-Alfa, Ghassan K., Ross, Jeffrey S., van de Ven, Marieke, Rottenberg, Sven, Cuppen, Edwin, Chessex, Anne Vaslin, Ali, Siraj M., Burn, Timothy C., Jimenez, Connie R., Ganesan, Shridar, Wessels, Lodewyk F. A., and Jonkers, Jos
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- 2022
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30. Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma
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Sangro, Bruno, primary, Galle, Peter R., additional, Kelley, Robin Kate, additional, Charoentum, Chaiyut, additional, De Toni, Enrico N., additional, Ostapenko, Yurii, additional, Heo, Jeong, additional, Cheng, Ann-Lii, additional, Wilson Woods, Andrea, additional, Gupta, Charu, additional, Abraham, Jayne, additional, McCoy, Carrie L., additional, Patel, Nikunj, additional, Negro, Alejandra, additional, Vogel, Arndt, additional, and Abou-Alfa, Ghassan K., additional
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- 2024
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31. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update Clinical Insights
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Rose, Michal G., primary, Kennedy, Erin B., additional, Abou-Alfa, Ghassan K., additional, Finn, Richard S., additional, Gade, Terence, additional, Kelley, R. Kate, additional, Taddei, Tamar, additional, and Gordan, John D., additional
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- 2024
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32. A framework for fibrolamellar carcinoma research and clinical trials
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Dinh, Timothy A., Utria, Alan F., Barry, Kevin C., Ma, Rosanna, Abou-Alfa, Ghassan K., Gordan, John D., Jaffee, Elizabeth M., Scott, John D., Zucman-Rossi, Jessica, O’Neill, Allison F., Furth, Mark E., and Sethupathy, Praveen
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- 2022
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33. An Open‐Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM‐080301 in Subjects with Advanced Hepatocellular Carcinoma
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Dika, Imane El, Lim, Ho Yeong, Yong, Wei Peng, Lin, Chia‐Chi, Yoon, Jung‐Hwan, Modiano, Manuel, Freilich, Bradley, Choi, Hye Jin, Chao, Tsu‐Yi, Kelley, Robin K, Brown, Joanne, Knox, Jennifer, Ryoo, Baek‐Yeol, Yau, Thomas, and Abou‐Alfa, Ghassan K
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Clinical Trials and Supportive Activities ,Liver Disease ,Digestive Diseases ,Cancer ,Rare Diseases ,Clinical Research ,Liver Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Administration ,Intravenous ,Adult ,Aged ,Antineoplastic Agents ,Carcinoma ,Hepatocellular ,Cohort Studies ,Dose-Response Relationship ,Drug ,Female ,Follow-Up Studies ,Humans ,Lipids ,Liver Neoplasms ,Male ,Maximum Tolerated Dose ,Middle Aged ,Nanoparticles ,Patient Safety ,Prognosis ,RNA ,Small Interfering ,Tissue Distribution ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted.
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- 2019
34. An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma.
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El Dika, Imane, Lim, Ho Yeong, Yong, Wei Peng, Lin, Chia-Chi, Yoon, Jung-Hwan, Modiano, Manuel, Freilich, Bradley, Choi, Hye Jin, Chao, Tsu-Yi, Kelley, Robin K, Brown, Joanne, Knox, Jennifer, Ryoo, Baek-Yeol, Yau, Thomas, and Abou-Alfa, Ghassan K
- Subjects
Humans ,Carcinoma ,Hepatocellular ,Liver Neoplasms ,Lipids ,RNA ,Small Interfering ,Antineoplastic Agents ,Prognosis ,Cohort Studies ,Follow-Up Studies ,Maximum Tolerated Dose ,Tissue Distribution ,Dose-Response Relationship ,Drug ,Adult ,Aged ,Middle Aged ,Female ,Male ,Nanoparticles ,Patient Safety ,Administration ,Intravenous ,Carcinoma ,Hepatocellular ,Dose-Response Relationship ,Drug ,Administration ,Intravenous ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted.
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- 2019
35. Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial
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Freemantle, Nick, Mollon, Patrick, Meyer, Tim, Cheng, Ann-Lii, El-Khoueiry, Anthony B., Kelley, Robin K., Baron, Ari D., Benzaghou, Fawzi, Mangeshkar, Milan, and Abou-Alfa, Ghassan K.
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- 2022
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36. Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child–Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial
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El-Khoueiry, Anthony B., Meyer, Tim, Cheng, Ann-Lii, Rimassa, Lorenza, Sen, Suvajit, Milwee, Steven, Kelley, Robin Kate, and Abou-Alfa, Ghassan K.
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- 2022
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37. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial
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Yau, Thomas, Park, Joong-Won, Finn, Richard S, Cheng, Ann-Lii, Mathurin, Philippe, Edeline, Julien, Kudo, Masatoshi, Harding, James J, Merle, Philippe, Rosmorduc, Olivier, Wyrwicz, Lucjan, Schott, Eckart, Choo, Su Pin, Kelley, Robin Kate, Sieghart, Wolfgang, Assenat, Eric, Zaucha, Renata, Furuse, Junji, Abou-Alfa, Ghassan K, El-Khoueiry, Anthony B, Melero, Ignacio, Begic, Damir, Chen, Gong, Neely, Jaclyn, Wisniewski, Tami, Tschaika, Marina, and Sangro, Bruno
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- 2022
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38. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma
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Abou-Alfa, Ghassan K, Meyer, Tim, Cheng, Ann-Lii, El-Khoueiry, Anthony B, Rimassa, Lorenza, Ryoo, Baek-Yeol, Cicin, Irfan, Merle, Philippe, Chen, YenHsun, Park, Joong-Won, Blanc, Jean-Frederic, Bolondi, Luigi, Klümpen, Heinz-Josef, Chan, Stephen L, Zagonel, Vittorina, Pressiani, Tiziana, Ryu, Min-Hee, Venook, Alan P, Hessel, Colin, Borgman-Hagey, Anne E, Schwab, Gisela, and Kelley, Robin K
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Digestive Diseases ,Rare Diseases ,Clinical Trials and Supportive Activities ,Clinical Research ,Liver Disease ,Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Aged ,80 and over ,Anilides ,Antineoplastic Agents ,Carcinoma ,Hepatocellular ,Disease-Free Survival ,Double-Blind Method ,Female ,Humans ,Kaplan-Meier Estimate ,Liver Neoplasms ,Male ,Middle Aged ,Pyridines ,Receptor Protein-Tyrosine Kinases ,Medical and Health Sciences ,General & Internal Medicine - Abstract
BackgroundCabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib as compared with placebo in previously treated patients with advanced hepatocellular carcinoma.MethodsA total of 707 patients were randomly assigned in a 2:1 ratio to receive cabozantinib (60 mg once daily) or matching placebo. Eligible patients had received previous treatment with sorafenib, had disease progression after at least one systemic treatment for hepatocellular carcinoma, and may have received up to two previous systemic regimens for advanced hepatocellular carcinoma. The primary end point was overall survival. Secondary end points were progression-free survival and the objective response rate.ResultsAt the second planned interim analysis, the trial showed significantly longer overall survival with cabozantinib than with placebo. Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P
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- 2018
39. Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma
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Javle, Milind, Lowery, Maeve, Shroff, Rachna T, Weiss, Karl Heinz, Springfeld, Christoph, Borad, Mitesh J, Ramanathan, Ramesh K, Goyal, Lipika, Sadeghi, Saeed, Macarulla, Teresa, El-Khoueiry, Anthony, Kelley, Robin Kate, Borbath, Ivan, Choo, Su Pin, Oh, Do-Youn, Philip, Philip A, Chen, Li-Tzong, Reungwetwattana, Thanyanan, Van Cutsem, Eric, Yeh, Kun-Huei, Ciombor, Kristen, Finn, Richard S, Patel, Anuradha, Sen, Suman, Porter, Dale, Isaacs, Randi, Zhu, Andrew X, Abou-Alfa, Ghassan K, and Bekaii-Saab, Tanios
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Orphan Drug ,Rare Diseases ,Clinical Research ,Digestive Diseases ,Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Administration ,Oral ,Adult ,Aged ,Antineoplastic Agents ,Bile Duct Neoplasms ,Biomarkers ,Tumor ,Cholangiocarcinoma ,Disease Progression ,Drug Administration Schedule ,Gene Amplification ,Gene Fusion ,Genetic Predisposition to Disease ,Humans ,Middle Aged ,Mutation ,Phenotype ,Phenylurea Compounds ,Progression-Free Survival ,Prospective Studies ,Protein Kinase Inhibitors ,Pyrimidines ,Receptor ,Fibroblast Growth Factor ,Type 2 ,Time Factors ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.
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- 2018
40. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update
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Gordan, John D., primary, Kennedy, Erin B., additional, Abou-Alfa, Ghassan K., additional, Beal, Eliza, additional, Finn, Richard S., additional, Gade, Terence P., additional, Goff, Laura, additional, Gupta, Shilpi, additional, Guy, Jennifer, additional, Hoang, Hang T., additional, Iyer, Renuka, additional, Jaiyesimi, Ishmael, additional, Jhawer, Minaxi, additional, Karippot, Asha, additional, Kaseb, Ahmed O., additional, Kelley, R. Kate, additional, Kortmansky, Jeremy, additional, Leaf, Andrea, additional, Remak, William M., additional, Sohal, Davendra P.S., additional, Taddei, Tamar H., additional, Wilson Woods, Andrea, additional, Yarchoan, Mark, additional, and Rose, Michal G., additional
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- 2024
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41. CALGB 80802 (Alliance): Impact of Sorafenib with and without Doxorubicin on Hepatitis C Infection in Patients with Advanced Hepatocellular Carcinoma
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Abou-Alfa, Ghassan K., primary, Geyer, Susan M., additional, Nixon, Andrew B., additional, Innocenti, Federico, additional, Shi, Qian, additional, Kumthekar, Priya, additional, Jacobson, Sawyer, additional, El Dika, Imane, additional, Yaqubie, Amin, additional, Lopez, Juan, additional, Huang, Binhui, additional, Tang, Yi-Wei, additional, Wen, Yujia, additional, Schwartz, Lawrence H., additional, El-Khoueiry, Anthony B., additional, Knox, Jennifer J., additional, Rajdev, Lakshmi, additional, Bertagnolli, Monica M., additional, Meyerhardt, Jeffrey A., additional, O'Reilly, Eileen M., additional, and Venook, Alan P., additional
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- 2024
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42. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma
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Sangro, B., primary, Chan, S.L., additional, Kelley, R.K., additional, Lau, G., additional, Kudo, M., additional, Sukeepaisarnjaroen, W., additional, Yarchoan, M., additional, De Toni, E.N., additional, Furuse, J., additional, Kang, Y.K., additional, Galle, P.R., additional, Rimassa, L., additional, Heurgué, A., additional, Tam, V.C., additional, Van Dao, T., additional, Thungappa, S.C., additional, Breder, V., additional, Ostapenko, Y., additional, Reig, M., additional, Makowsky, M., additional, Paskow, M.J., additional, Gupta, C., additional, Kurland, J.F., additional, Negro, A., additional, Abou-Alfa, G.K., additional, Azevedo, Sergio, additional, Braghiroli, Maria Ignez, additional, Girotto, Gustavo, additional, Bragagnoli, Arinilda, additional, Branco, Ricardo, additional, Faccio, Adilson, additional, Moretto, Andrea, additional, Skare, Nils, additional, Dutra, Jamille, additional, Viola, Luciana, additional, Vianna, Karina, additional, Meton, Fernando, additional, Sette, Claudia, additional, Faulhaber, Amanda, additional, Tam, Vincent C., additional, Couture, Felix, additional, Biagi, Jim, additional, Castel, Helene, additional, Mulder, Karen, additional, Ko, Yoo-Joung, additional, Zbuk, Kevin, additional, Welch, Stephen, additional, Beaudoin, Annie, additional, Heurgué, Alexandra, additional, Assenat, Eric, additional, Archambeaud, Isabelle, additional, Tougeron, David, additional, Peron, Jean-Marie, additional, Gilabert, Marine, additional, Bronowicki, Jean-Pierre, additional, Cattan, Stephane, additional, Blanc, Jean-Frederic, additional, Bouattour, Mohamed, additional, Phelip, Jean-Marc, additional, Boige, Valerie, additional, Michel, Pierre, additional, Frin, Anne-Claire, additional, Enrico N De Toni, Germany, additional, Berres, Marie-Luise, additional, Vogel, Arndt, additional, Berg, Thomas, additional, Ettrich, Thomas, additional, Waldschmidt, Dirk, additional, Wedemeyer, Hans Heinrich, additional, Worns, Marcus-Alexander, additional, Bitzer, Michael, additional, Weiss, Karl-Heinz, additional, Lau, George, additional, Chan, Stephen L., additional, Yau, Thomas, additional, Tai, Yin Ping, additional, Lee, Ann Shing, additional, Thungappa, Satheesh Chiradoni, additional, N, Lokesh K., additional, Ostwal, Vikas Sureshchand, additional, Ashok, Kattimani Kiran, additional, Mittal, Sushant, additional, Goyal, Hari, additional, Srinivasan, Sankar, additional, Biswas, Ghanashyam, additional, Mohan, Mallavarapu, additional, Limaye, Sewanti, additional, Asarawala, Nirav, additional, Rimassa, Lorenza, additional, Falcone, Alfredo, additional, Gianni, Luca, additional, Gasbarrini, Antonio, additional, Daniele, Bruno, additional, Avallone, Antonio, additional, Paolo Frassineti, Giovanni Luca, additional, Roila, Fausto, additional, Kudo, Masatoshi, additional, Kawaoka, Tomokazu, additional, Morimoto, Manabu, additional, Takikawa, Yasuhiro, additional, Kato, Naoya, additional, Yamashita, Tatsuya, additional, Osaki, Yukio, additional, Motomura, Kenta, additional, Tateishi, Ryosuke, additional, Ohkawa, Kazuyoshi, additional, Wada, Yoshiyuki, additional, Onishi, Hideki, additional, Sasahira, Naoki, additional, Inaba, Yoshitaka, additional, Kurosaki, Masayuki, additional, Tsuji, Kunihiko, additional, Takei, Yoshiyuki, additional, Aramaki, Takeshi, additional, Hagihara, Atsushi, additional, Furuse, Junji, additional, Kioka, Kiyohide, additional, Koga, Hironori, additional, Sasaki, Yutaka, additional, Numata, Kazushi, additional, Tada, Toshifumi, additional, Kawaguchi, Yasunori, additional, Nadano, Seijin, additional, Alexander Vasilyev, Russian Federation, additional, Breder, Valery, additional, Lipatov, Oleg, additional, Dvorkin, Mikhail, additional, Zarubenkov, Oleg, additional, Kutukova, Svetlana, additional, Ponomarev, Roman, additional, Shostka, Kirill, additional, Alyasova, Anna, additional, Topuzov, Eldar, additional, Severtsev, Alexey, additional, Petrov, Yuryi, additional, Erygin, Dmitriy, additional, Berdov, Boris, additional, Kang, Yoon-Koo, additional, Tak, Won-Young, additional, Park, Joong-Won, additional, Lim, Ho Yeong, additional, Heo, Jeong, additional, Kim, Jee Hyun, additional, Kim, Tae-You, additional, Choi, Hye Jin, additional, Varela, María, additional, Reig Monzon, María Elisa, additional, Sangro, Bruno, additional, Martin, Carlos Gómez, additional, Ponce, Carmen Guillén, additional, López, Carlos, additional, Cheng, Ann-Lii, additional, Chao, Yee, additional, Feng, Yin-Hsun, additional, Jeng, Long-Bin, additional, Hung, Chao-Hung, additional, Hou, Ming-Mo, additional, Wang Tsang-En Wang, Jing-Houng, additional, Yen, Chia-Jui, additional, Sukeepaisarnjaroen, Wattana, additional, Sunpaweravong, Patrapim, additional, Charoentum, Chaiyut, additional, Tanasanvimon, Suebpong, additional, Sirachainan, Ekaphop, additional, Ungtrakul, Teerapat, additional, Prasongsook, Naiyarat, additional, Maneenil, Kunlatida, additional, Jitpewngarm, Wittawat, additional, Ostapenko, Yurii, additional, Skoryi, Denys, additional, Bondarenko, Igor, additional, Shparyk, Yaroslav, additional, Trukhin, Dmytro, additional, Hotko, Yevhen, additional, Ursol, Grygorii, additional, Kryzhanivska, Anna, additional, Abou-Alfa, Ghassan K., additional, Mody, Kabir, additional, Dayyani, Farshid, additional, Al-Rajabi, Raed, additional, Yarchoan, Mark, additional, Gandhi, Sunil, additional, Crysler, Oxana, additional, He, Aiwu Ruth, additional, Reeves, James, additional, Bahary, Nathan, additional, Mahipal, Amit, additional, Kelley, Robin Kate, additional, Dasgupta, Anirudha, additional, Rowe, Julie, additional, Thota, Ramya, additional, Beg, Muhammad, additional, Morse, Michael, additional, Choi, Sung-hee, additional, Crocenzi, Todd, additional, Somer, Bradley, additional, Abrams, Thomas, additional, Denlinger, Crystal, additional, Zhang, Yue, additional, Sharma, Nisha, additional, Dao, Tu V., additional, Thinh, Nguyen Tien, additional, and Tuyet Phuong, Le Thi, additional
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- 2024
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43. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study
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Yoo, Changhoon, Kim, Kyu-pyo, Jeong, Jae Ho, Kim, Ilhwan, Kang, Myoung Joo, Cheon, Jaekyung, Kang, Byung Woog, Ryu, Hyewon, Lee, Ji Sung, Kim, Kyung Won, Abou-Alfa, Ghassan K, and Ryoo, Baek-Yeol
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- 2021
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44. Safety and feasibility of preoperative simultaneous portal vein embolization and biliary drainage in hilar cholangiocarcinoma prior to hepatectomy
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Soliman, Mohamed M., primary, Chevallier, Olivier, primary, Velayati, Sara, primary, Zhao, Ken, primary, Marinelli, Brett, primary, Ridouani, Fourat, primary, Karimi, Anita, primary, Covey, Anne, primary, Erinjeri, Joseph P., primary, Schattner, Mark, primary, Harding, James J., primary, Abou-Alfa, Ghassan K., primary, Wei, Alice C., primary, Soares, Kevin C., primary, Jarnagin, William, primary, and Yarmohammadi, Hooman, primary
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- 2024
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45. PROOF 301: Results of an early discontinued randomized phase 3 trial of the oral FGFR inhibitor infigratinib vs. gemcitabine plus cisplatin in patients with advanced cholangiocarcinoma (CCA) with an FGFR2 gene fusion/rearrangement.
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Abou-Alfa, Ghassan K., primary, Borbath, Ivan, additional, Roychowdhury, Sameek, additional, Goyal, Lipika, additional, Lamarca, Angela, additional, Macarulla, Teresa, additional, Shroff, Rachna T., additional, Oh, Do-Youn, additional, Javle, Milind M., additional, Tamas, Catalin, additional, Savastano, David M, additional, Van Veenhuyzen, David Friedrich, additional, Xu, Cindy, additional, Solanas, Jacki, additional, and Freas, Elizabeth, additional
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- 2024
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46. Intrahepatic cholangiocarcinoma: Recurrence patterns, genomics and survival.
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Chandra, Pratik, primary, Song, Yi, additional, Drill, Esther N., additional, Wei, Alice Chia-Chi, additional, Kemeny, Nancy E., additional, Cercek, Andrea, additional, Connell, Louise Catherine, additional, Harding, James J., additional, Abou-Alfa, Ghassan K., additional, Park, Wungki, additional, Kingham, T. Peter, additional, Soares, Kevin, additional, Balachandran, Vinod P., additional, Drebin, Jeffrey A., additional, D'Angelica, Michael Ian, additional, O'Reilly, Eileen Mary, additional, Groot Koerkamp, Bas, additional, and Jarnagin, William R., additional
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- 2024
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47. Novel Non-Protein Biomarkers for Early Detection of Hepatocellular Carcinoma
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Abou-Alfa, Ghassan K., Wu, Lin, and Villanueva, Augusto
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- 2021
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48. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study
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Javle, Milind, Roychowdhury, Sameek, Kelley, Robin Kate, Sadeghi, Saeed, Macarulla, Teresa, Weiss, Karl Heinz, Waldschmidt, Dirk-Thomas, Goyal, Lipika, Borbath, Ivan, El-Khoueiry, Anthony, Borad, Mitesh J, Yong, Wei Peng, Philip, Philip A, Bitzer, Michael, Tanasanvimon, Surbpong, Li, Ai, Pande, Amit, Soifer, Harris S, Shepherd, Stacie Peacock, Moran, Susan, Zhu, Andrew X, Bekaii-Saab, Tanios S, and Abou-Alfa, Ghassan K
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- 2021
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49. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study
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Javle, Milind, Borad, Mitesh J, Azad, Nilofer S, Kurzrock, Razelle, Abou-Alfa, Ghassan K, George, Ben, Hainsworth, John, Meric-Bernstam, Funda, Swanton, Charles, Sweeney, Christopher J, Friedman, Claire F, Bose, Ron, Spigel, David R, Wang, Yong, Levy, Jonathan, Schulze, Katja, Cuchelkar, Vaikunth, Patel, Arisha, and Burris, Howard
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- 2021
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50. ASO Visual Abstract: Recurrence of Hepatocellular Carcinoma After Complete Radiologic Response to Trans-Arterial embolization: A Retrospective Study on Patterns, Treatments, and Prognosis
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Ilagan, Crisanta H., Goldman, Debra A., Gönen, Mithat, Aveson, Victoria G., Babicky, Michelle, Balachandran, Vinod P., Drebin, Jeffrey A., Jarnagin, William R., Wei, Alice C., Kingham, T. Peter, Abou-Alfa, Ghassan K., Brown, Karen T., and D’Angelica, Michael I.
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- 2022
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Catalog
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