Author: Masatoshi Kudo, Peter R. Galle, Giovanni Brandi, Yoon-Koo Kang, Chia-Jui Yen, Richard S. Finn, Josep M. Llovet, Eric Assenat, Philippe Merle, Stephen L. Chan, Daniel H. Palmer, Masafumi Ikeda, Tatsuya Yamashita, Arndt Vogel, Yi-Hsiang Huang, Paolo B. Abada, Reigetsu Yoshikawa, Kenta Shinozaki, Chunxiao Wang, Ryan C. Widau, Andrew X. Zhu
Abstract: Abstract: Background & Aims. The albumin-bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). This post-hoc analysis assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using ALBI score in patients with advanced HCC. Methods. Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomized in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2 weeks. Data were analyzed by trial and as a meta-analysis of individual patient-level data (pooled population) from REACH (alpha-fetoprotein ≥400 ng/mL) and REACH-2. Patients from REACH with Child-Pugh class B were analyzed as a separate cohort. ALBI grade and score were calculated at baseline and before each treatment cycle. Results. Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; Hazard ratio: 1.38 [1.13-1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared to baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumor response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445-0.824]) and ALBI grade 2 (HR 0.814 [0.630-1.051]). Conclusions. Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade. Keywords: ALBI; Liver function; Prognosis; Safety; Survival; Tumor response
