IMPORTANCE REACH is the first phase 3 trial to provide information on hepatocellular cancer (HCC) in the second-line (postsorafenib) setting categorized by Child-Pugh score, a scoring system used to measure the severity of chronic liver disease. This exploratory analysis demonstrates the relationship between a potential ramucirumab survival benefit, severity of liver disease, and baseline α-fetoprotein (αFP). OBJECTIVE To assess treatment effects and tolerability of ramucirumab by Child-Pugh score in patients with HCC enrolled in the REACH trial. DESIGN, SETTINGS, AND PARTICIPANTS Randomized, double-blind, phase 3 trial of ramucirumab and best supportive care vs placebo and best supportive care as second-line treatment in patients with HCC enrolled between November 4, 2010 and April 18, 2013, from 154 global sites. Overall, 643 patients were randomized and included in this analysis 565 patients considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients considered class B (Child-Pugh scores 7 and 8). INTERVENTIONS Ramucirumab (8mg/kg) or placebo intravenously plus best supportive care every 2 weeks. MAIN OUTCOMES AND MEASURES Overall survival (OS), defined as time from randomization to death from any cause. RESULTS In the randomized population of 643 patients (mean [SD] age, 62.8 [11.1] years) in this analysis, a potential ramucirumab OS benefit was observed for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80 95%CI, 0.63-1.02 P = .06) but no apparent benefit for patients with Child-Pugh scores of 6 or 7 and 8. In patients with baseline αFP levels of 400 ng/mL (to convert ng/mL to μg/L, multiply by 1.0) or more, a ramucirumab OS benefit was significant for a score of Child-Pugh 5 (HR, 0.61 95%CI, 0.43-0.87 P = .01) and Child-Pugh 6 (HR, 0.64 95%CI, 0.42-0.98 P = .04), but was not significant for Child-Pugh 7 and 8. The overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable. Regardless of treatment arm, patients with Child-Pugh scores of 7 and 8 experienced a higher incidence of grade 3 or higher treatment-emergent adverse events, including ascites and asthenia, and special-interest events, including liver injury and/or failure and bleeding, compared with patients with Child-Pugh scores of 5 or 6. CONCLUSIONS AND RELEVANCE In unselected patients, a trend for ramucirumab survival benefit was observed only for patients with a Child-Pugh score of 5. In patients with baseline αFP levels of 400 ng/mL or more, a ramucirumab survival benefit was observed for Child-Pugh scores of 5 and 6. Ramucirumab had a manageable toxic effect profile. These results support the ongoing REACH-2 study of ramucirumab in patients with advanced HCC with underlying Child-Pugh A cirrhosis and baseline αFP levels of 400 ng/mL or more.