Efficacy and Safety of Ramucirumab in Asian and Non-Asian Patients with Advanced Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Individual Data Analysis of Two Randomized Studies

Chia-Jui Yen; Masatoshi Kudo; Ho-Yeong Lim; Chih-Hung Hsu; Arndt Vogel; Giovanni Brandi; Rebecca Cheng; Ioana Simona Nitu; Paolo Abada; Yanzhi Hsu; Andrew X Zhu; Yoon-Koo Kang

doi:10.1159/000506946

Efficacy and Safety of Ramucirumab in Asian and Non-Asian Patients with Advanced Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Individual Data Analysis of Two Randomized Studies

Liver Cancer. 2020 Aug;9(4):440-454. doi: 10.1159/000506946. Epub 2020 May 5.

Authors

Chia-Jui Yen¹, Masatoshi Kudo², Ho-Yeong Lim³, Chih-Hung Hsu⁴, Arndt Vogel⁵, Giovanni Brandi⁶, Rebecca Cheng⁷, Ioana Simona Nitu⁸, Paolo Abada⁹, Yanzhi Hsu¹⁰, Andrew X Zhu¹¹, Yoon-Koo Kang¹²

Affiliations

¹ Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
³ Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
⁴ National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
⁵ Hannover Medical School, Hannover, Germany.
⁶ Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
⁷ Eli Lilly and Company, Taipei, Taiwan.
⁸ Eli Lilly and Company, Bucharest, Romania.
⁹ Eli Lilly and Company, Indianapolis, Indiana, USA.
¹⁰ TG Therapeutics Inc., New York, New York, USA.
¹¹ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
¹² Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Abstract

Objective: REACH-2 and REACH were randomized, placebo-controlled, double-blind, multicenter phase 3 trials which showed survival benefits of ramucirumab treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP). We evaluated the efficacy and safety of ramucirumab in Asian and non-Asian patients with AFP ≥400 ng/mL from REACH-2 and REACH.

Methods: We pooled Asian and non-Asian patients from the REACH-2 and REACH trials and performed an individual patient data meta-analysis. Overall survival (OS) and progression-free survival were evaluated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated with a stratified Cox regression model.

Results: In the pooled REACH-2 and REACH patient population, 291 Asian patients were randomly assigned to receive ramucirumab (n = 168) or placebo (n = 123), and 251 non-Asian patients received ramucirumab (n = 148) or placebo (n = 103). The median OS was significantly longer in the ramucirumab arm in comparison to the placebo arm for Asian patients (8.08 vs. 4.76 months, stratified HR 0.73 [95% CI 0.56-0.95], p = 0.0189) and non-Asian patients (7.98 vs. 5.22 months, stratified HR 0.65 [95% CI 0.49-0.86], p = 0.0028). The overall response rate (ORR) and disease control rate (DCR) were significantly higher in the ramucirumab arm compared to the placebo arm for Asian patients (ORR: 4.2 vs. 0.8%; DCR: 53.6 vs. 33.3%) and non-Asian patients (ORR: 6.8 vs. 1.0%; DCR: 59.5 vs. 41.7%). The most common grade ≥3 treatment-emergent adverse events reported in the ramucirumab arm were hypertension (7.7%), decreased appetite (1.2%), and ascites (1.2%) for Asian patients and hypertension (16.9%), ascites (8.8%), asthenia (4.7%), and fatigue (5.4%) for non-Asian patients.

Discussion and conclusion: This pooled analysis of the REACH-2/REACH trials demonstrates significant benefits, with a manageable safety profile, of ramucirumab treatment in Asian and non-Asian patients with advanced HCC and baseline AFP ≥400 ng/mL.

Keywords: Asian patients; Hepatocellular carcinoma; Ramucirumab.