Efficacy and safety of ramucirumab (RAM) in Asian and non-Asian patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP): Subgroup analysis from two randomized studies

Abstract

Background: The etiological factors and management of HCC vary by geographical region . REACH-2 and REACH showed significant survival benefits of RAM treatment for HCC in patients (pts) with baseline AFP ≥400 ng/mL. We conducted a pooled subgroup analysis to investigate the efficacy and safety of RAM in Asian and non-Asian pts from REACH-2 and REACH (high AFP subpopulation). Methods: Pts were randomized to receive RAM 8 mg/kg IV or placebo (PL) once every two weeks, plus best supportive care, until disease progression or unacceptable toxicity. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS. Efficacy analyses were stratified by study. Results: Across the two studies, 291 Asian pts were randomized to RAM (168) or PL (123); 251 non-Asian pts were randomized to RAM (148) or PL (103). Baseline characteristics were generally balanced between treatment arms in Asian and non-Asian patients. RAM significantly improved median OS in Asian pts; 8.08 months (m) RAM vs 4.76 m PL (stratified hazard ratio [HR] 0.73, 95% confidence interval [CI]: 0.56, 0.95), and non-Asian pts; 7.98 m RAM vs 5.22 m PL (HR 0.65, 95% CI: 0.49, 0.86). RAM significantly improved median PFS in Asian pts; 2.73 m RAM vs 1.45 m PL (HR 0.58, 95% CI: 0.44, 0.76), and non- Asian pts; 3.06 m RAM vs 1.87 m PL (HR 0.55, 95% CI: 0.41, 0.73). ORR was 4.2% RAM vs 0.8% PL (Asian pts) and 6.8% RAM vs 1.0% PL (non-Asian pts); DCR was 53.6% RAM vs 33.3% PL (Asian pts) and 59.5% RAM vs 41.7% PL (non-Asian pts). The most common grade ≥3 adverse event occurring in the RAM arm of Asian and non-Asian pts was hypertension (7.7% and 16.9%, respectively). Conclusions: This subgroup analysis demonstrates survival benefits of RAM treatment in Asian and non-Asian patients with advanced HCC and AFP ≥400 ng/mL. Treatment was well tolerated, with similar safety profiles between Asian and non-Asian pts.