Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Analysis of REACH pts by Child-Pugh (CP) score.

4108 Background: REACH was a global, randomized, double-blind, phase III study evaluating the efficacy and safety of RAM as a single-agent treatment of pts with advanced HCC after prior sorafenib therapy. The primary outcome for the ITT population was presented at ESMO 2014. The overall survival (OS) HR for the ITT population (RAM 283; placebo [PBO] 282) was 0.866 (95% CI 0.717, 1.046; p = 0.1391). In pts with baseline alpha-fetoprotein (AFP) ≥ 400 ng/mL (RAM 119; PBO 131), OS HR was 0.67 (95% CI 0.51–0.90; p = 0.0059). Methods: Efficacy and safety of RAM based on CP score are presented for all pts enrolled in REACH inclusive of ITT (n = 565) and CP B (n = 78) population. Results: In REACH, pts with CP5 (N = 177 RAM, N = 180 PBO), CP6 (N = 108 RAM, N = 100 PBO), and CP7+8 (CPB) (N = 39 RAM, N = 39 PBO) were enrolled. Baseline pt characteristics were generally balanced between treatment arms by CP score. The table below shows OS, PFS, ORR and DCR according to CP score. The safety profile of RAM in pts with CP5 and CP6 was similar, and consistent with that observed in the ITT analysis of CP A pts. In pts with CP7+8 (CP B), an increase in liver events grade ≥ 3 was observed on the RAM vs PBO arm (56% vs 41%), including an increase in hepatic encephalopathy grade ≥ 3 (10% vs 0%). This observation led to exclusion of CP B pts from enrollment after 441 total pts were randomized during the study. Conclusions: A greater RAM treatment benefit was observed in pts with lower CP scores. In the CP B pt population, an increase in liver adverse events was observed for RAM, specifically hepatic encephalopathy. A consistent and clinically meaningful improvement in OS, regardless of CP score, was observed in pts with elevated baseline AFP levels ( ≥ 400 ng/mL). Clinical trial information: NCT01140347. CP A CP A CP B CP5 CP6 CP7+8 REACH efficacy population OS HR 95% CI p 0.796 0.625, 1.015 0.0647 0.955 0.712, 1.280 0.7609 0.998 0.623, 1.599 0.9946 PFS HR 95% CI p 0.587 0.469, 0.735 < 0.0001 0.778 0.581, 1.041 0.0912 0.738 0.457, 1.194 0.2219 ORR RAM 8.5% 5.6% 0% PBO 0.6% 1.0% 2.6% DCR RAM 62.1% 47.2% 48.7% PBO 46.1% 45.0% 28.2% REACH pts with baseline AFP ≥ 400 ng/mL* OS HR 95% CI p 0.611 0.429, 0.870 0.0058 0.639 0.418, 0.978 0.0384 0.674 0.332, 1.368 0.2756