Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial

Masatoshi Kudo; Ho Yeong Lim; Ann-Lii Cheng; Yee Chao; Thomas Yau; Sadahisa Ogasawara; Masayuki Kurosaki; Naoki Morimoto; Kazuyoshi Ohkawa; Tatsuya Yamashita; Kyung-Hun Lee; Erluo Chen; Abby B Siegel; Baek-Yeol Ryoo

doi:10.1159/000515553

Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial

Liver Cancer. 2021 Jun;10(3):275-284. doi: 10.1159/000515553. Epub 2021 Apr 27.

Authors

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

Affiliations

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.

Keywords: Hepatocellular carcinoma; Pembrolizumab; Programmed death 1.