Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha‐fetoprotein after sorafenib in REACH and REACH‐2

作者：Masatoshi Kudo, Peter R. Galle, Josep M. Llovet, Richard S. Finn, Arndt Vogel, Kenta Motomura, Eric Assénat, Philippe Merle, Giovanni Brandi, Bruno Daniele, Takuji Okusaka, Jiří Tomášek, Christophe Borg, Vincenzo Dadduzio, Manabu Morimoto, Marc Pracht, Min‐Hua Jen, N. Drove Ubreva, Ryan C. Widau, Kenta Shinozaki, Reigetsu Yoshikawa, Andrew X. Zhu · 发表于：Liver International · 年份：2020 · DOI：10.1111/liv.14462 · 被引用次数：31 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Liver Disease Diagnosis and Treatment、Cholangiocarcinoma and Gallbladder Cancer Studies

BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866) and ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A tren...