Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab

BACKGROUND & AIMS: Radiological progression patterns to first‐line sorafenib have been associated with post‐progression and overall survival in advanced hepatocellular carcinoma, but these associations remain unknown for therapies in second‐ and later‐line settings. This post hoc analysis of REACH and REACH‐2 examined outcomes by radiological progression patterns in the second‐line setting of patients with advanced hepatocellular carcinoma treated with ramucirumab or placebo. METHODS: Patients with advanced hepatocellular carcinoma, Child‐Pugh A and Eastern Cooperative Oncology Group Performance Status 0 or 1 with prior sorafenib were randomized to receive ramucirumab 8mg/kg or placebo every 2 weeks. Among 625 patients with ≥1 progression pattern (new extrahepatic lesion [including new macrovascular invasion], new intrahepatic lesion, extrahepatic growth or intrahepatic growth), data were analysed by trial and for pooled individual patient data for REACH‐2 and REACH (alpha‐fetoprotein ≥400 ng/mL). Cox models evaluated prognostic implications of progression patterns on overall and post‐progression survival. RESULTS: Post‐progression survival was worse among those with new extrahepatic lesions in REACH (HR 2.33, 95% CI 1.51‐3.60), REACH‐2 (HR 1.49, 95% CI 0.72‐3.08) and the pooled population (HR 1.75, 95% CI 1.12‐2.74) compared to other progression patterns. Overall survival was also significantly reduced in those with new extrahepatic lesions across studies. Ramucirumab provided an overall survival benefit across progression patterns, including patients with new extrahepatic lesions (HR 0.56, 95% CI 0.39‐0.80) in the pooled population. CONCLUSIONS: The emergence of new extrahepatic lesions in the second‐line setting is a poor prognostic factor for post‐progression survival. The benefit of ramucirumab for overall survival was consistent across progression patterns.