Masatoshi Kudo1, Ho Yeong Lim2, Ann-Lii Cheng3, Yee Chao4, Thomas Yau5, Sadahisa Ogasawara6, Masayuki Kurosaki7, Naoki Morimoto8, Kazuyoshi Ohkawa9, Tatsuya Yamashita10, Kyung-Hun Lee11, Erluo Chen12, Abby B Siegel12, Baek-Yeol Ryoo13. 1. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan. 2. Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea. 3. Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan. 4. Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan. 5. Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China. 6. Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Japan. 7. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan. 8. Department of Gastroenterology, Jichi Medical University Hospital, Tochigi, Japan. 9. Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan. 10. Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan. 11. Department of Internal Medicine Seoul National University Hospital, Seoul, Republic of Korea. 12. Department of Medical Oncology, Merck & Co., Inc, Kenilworth, New Jersey, USA. 13. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Abstract
INTRODUCTION: KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. METHODS: Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. RESULTS: The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6-4.1) versus 1.4 months (95% CI 1.4-2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32-0.70). The median OS was 13.8 months (95% CI 10.1-16.9) for pembrolizumab versus 8.3 months (95% CI 6.3-11.8) for placebo (HR 0.55; 95% CI 0.37-0.80). ORR was 20.6% (95% CI 13.4-29.5) for pembrolizumab versus 2.0% (95% CI 0.1-10.6) for placebo (difference: 18.5%; 95% CI 8.3-27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3-5 TRAEs, respectively. No treatment-related deaths occurred. CONCLUSION: Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.
INTRODUCTION: KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. METHODS: Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. RESULTS: The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6-4.1) versus 1.4 months (95% CI 1.4-2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32-0.70). The median OS was 13.8 months (95% CI 10.1-16.9) for pembrolizumab versus 8.3 months (95% CI 6.3-11.8) for placebo (HR 0.55; 95% CI 0.37-0.80). ORR was 20.6% (95% CI 13.4-29.5) for pembrolizumab versus 2.0% (95% CI 0.1-10.6) for placebo (difference: 18.5%; 95% CI 8.3-27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3-5 TRAEs, respectively. No treatment-related deaths occurred. CONCLUSION: Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.
Authors: Richard S Finn; Shukui Qin; Masafumi Ikeda; Peter R Galle; Michel Ducreux; Tae-You Kim; Masatoshi Kudo; Valeriy Breder; Philippe Merle; Ahmed O Kaseb; Daneng Li; Wendy Verret; Derek-Zhen Xu; Sairy Hernandez; Juan Liu; Chen Huang; Sohail Mulla; Yulei Wang; Ho Yeong Lim; Andrew X Zhu; Ann-Lii Cheng Journal: N Engl J Med Date: 2020-05-14 Impact factor: 91.245
Authors: Andrew X Zhu; Richard S Finn; Julien Edeline; Stephane Cattan; Sadahisa Ogasawara; Daniel Palmer; Chris Verslype; Vittorina Zagonel; Laetitia Fartoux; Arndt Vogel; Debashis Sarker; Gontran Verset; Stephen L Chan; Jennifer Knox; Bruno Daniele; Andrea L Webber; Scot W Ebbinghaus; Junshui Ma; Abby B Siegel; Ann-Lii Cheng; Masatoshi Kudo Journal: Lancet Oncol Date: 2018-06-03 Impact factor: 41.316
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: Andrew X Zhu; Yoon-Koo Kang; Chia-Jui Yen; Richard S Finn; Peter R Galle; Josep M Llovet; Eric Assenat; Giovanni Brandi; Marc Pracht; Ho Yeong Lim; Kun-Ming Rau; Kenta Motomura; Izumi Ohno; Philippe Merle; Bruno Daniele; Dong Bok Shin; Guido Gerken; Christophe Borg; Jean-Baptiste Hiriart; Takuji Okusaka; Manabu Morimoto; Yanzhi Hsu; Paolo B Abada; Masatoshi Kudo Journal: Lancet Oncol Date: 2019-01-18 Impact factor: 41.316
Authors: Stephen V Liu; Misako Nagasaka; Victoria Stefaniak; Kristi Gruver; Yong Lin; David Ferry; Mark A Socinski; Li Zhang Journal: Front Oncol Date: 2022-06-10 Impact factor: 5.738