Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology

Peter R. Galle, Masatoshi Kudo, Josep M. Llovet, Richard S. Finn, Mark Karwal, Denis Pezet, Tae You Kim, Tsai Sheng Yang, Sara Lonardi, Jiri Tomasek, Jean Marc Phelip, Yann Touchefeu, Su Jin Koh, Guido Stirnimann, Kun Liang, Kenyon D. Ogburn, Chunxiao Wang, Paolo Abada, Ryan C. Widau, Andrew X. Zhu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background & Aims: Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH-2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load. Methods: Meta-analysis was conducted in patients with aHCC and alpha-fetoprotein (AFP) ≥400 ng/mL (N = 542) from REACH/REACH-2 trials. Individual patient-level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre-treatment serum HBV DNA and HCV RNA were quantified using Roche COBAS AmpliPrep/COBAS TaqMan. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazard model (stratified by study). Results: Baseline characteristics were generally balanced between arms in each subgroup (HBV: N = 225, HCV: N = 127, Other: N = 190). No significant difference in treatment effect by aetiology subgroup was detected (OS interaction P-value =.23). Median OS (ramucirumab vs placebo) in months was 7.7 versus 4.5 (HR 0.74, 95% CI 0.55–0.99) for HBV, 8.2 versus 5.5 (HR 0.82, 95% CI 0.55–1.23) for HCV and 8.5 versus 5.4 (HR 0.56, 95% CI 0.40–0.79) for Other. Ramucirumab showed similar overall safety profiles across subgroups. Worst outcomes were noted in patients with a detectable HBV load. Use of HBV antiviral therapy, irrespective of viral load, was beneficial for survival, liver function and liver-specific adverse events. Conclusions: Ramucirumab improved survival across aetiology subgroups with a tolerable safety profile, supporting its use in patients with aHCC and elevated AFP.

Original languageEnglish
Pages (from-to)2759-2767
Number of pages9
JournalLiver International
Issue number11
StatePublished - Nov 2021


  • hepatitis B
  • hepatitis C
  • hepatocellular carcinoma
  • ramucirumab


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