Ramucirumab for advanced hepatocellular carcinoma in the current real world: a Japanese single-arm study post-REACH-2 (The R-evolution study)

Invest New Drugs. 2024 Aug;42(4):394-404. doi: 10.1007/s10637-024-01441-3. Epub 2024 Jun 6.

Abstract

This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.

Keywords: Hepatocellular carcinoma; REACH-2 trial; Ramucirumab; Real-world data.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • East Asian People
  • Female
  • Humans
  • Japan
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use
  • Progression-Free Survival
  • Prospective Studies
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • Ramucirumab*

Substances

  • Ramucirumab
  • Antibodies, Monoclonal, Humanized
  • lenvatinib
  • Quinolines
  • Phenylurea Compounds
  • Antineoplastic Agents
  • Bevacizumab