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
Journal
Liver Cancer
Journal Volume
9
Journal Issue
4
Pages
440-454
Date Issued
2020
Author(s)
Yen C.-J.
Kudo M.
Lim H.-Y.
Vogel A.
Brandi G.
Cheng R.
Nitu I.S.
Abada P.
Hsu Y.
Zhu A.X.
Kang Y.-K.
Abstract
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. ? 2020 S. Karger AG. All rights reserved.
SDGs
Other Subjects
alpha fetoprotein; placebo; ramucirumab; sorafenib; abdominal pain; adult; advanced cancer; African American; aged; Article; ascites; Asian; asthenia; Black person; bleeding; Caucasian; clinical trial; controlled study; decreased appetite; disease control; double blind procedure; drug efficacy; drug safety; drug withdrawal; epistaxis; ethnicity; fatigue; female; gastrointestinal hemorrhage; headache; human; hypertension; infusion related reaction; liver cell carcinoma; liver injury; major clinical study; male; multicenter study (topic); nausea; overall response rate; overall survival; patient coding; peripheral edema; phase 3 clinical trial (topic); priority journal; progression free survival; proteinuria; randomized controlled trial (topic); thromboembolism; treatment duration; wound hemorrhage
Publisher
S. Karger AG
Type
journal article