Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2).

Abstract

BACKGROUND:

Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed.

METHODS:

A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0-1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score.

RESULTS:

Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546-1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23-0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59-0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages.

CONCLUSIONS:

Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.

• Authors: Masatoshi Kudo, Richard S Finn, Manabu Morimoto, Kun-Ming Rau, Masafumi Ikeda, Chia-Jui Yen, Peter R Galle, Josep M Llovet, Bruno Daniele, Ho Yeong Lim, David W McIlwain, Reigetsu Yoshikawa, Kenichi Nakamura, Kun Liang, Chunxiao Wang, Paolo Abada, Ryan C Widau, Andrew X Zhu
• Journal: Liver cancer (Liver Cancer) Vol. 10 Issue 5 Pg. 451-460 (Sep 2021) ISSN: 2235-1795 [Print] Switzerland
• PMID: 34721507 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 by S. Karger AG, Basel.