Ramucirumab is an effective treatment for patients with advanced HCC (aHCC) and baseline AFP {greater than or equal to}400 ng/mL. We aimed to identify prognostic and predictive factors of response to ramucirumab in patients with aHCC with AFP {greater than or equal to}400 ng/mL from the Phase III REACH and REACH-2 randomized trials.
Patients with aHCC, Child-Pugh class A with prior sorafenib treatment were randomized in REACH and REACH-2 (ramucirumab 8 mg/kg or placebo, biweekly). Meta-analysis of individual patient-level data (pooled population) from REACH (AFP {greater than or equal to}400 ng/mL) and REACH-2 was performed. A drug exposure analysis was conducted for those with evaluable pharmacokinetics data. To identify potential prognostic factors for overall survival (OS), multivariate analyzes were performed using a Cox proportional hazard regression model. To define predictors of ramucirumab benefit, subgroup-by-treatment interactions terms were evaluated.
Of 542 patients (316 ramucirumab, 226 placebo) analyzed, 8 variables had independent prognostic value associated with poor outcome (geographical region, ECOG PS {greater than or equal to}1, AFP >1000 ng/mL, Child-Pugh >A5, extrahepatic spread, high neutrophil-to-lymphocyte, high alkaline phosphatase and aspartate aminotransferase). Ramucirumab benefit was present across all subgroups, including patients with very aggressive HCC (above median AFP; HR: 0.64; 95%CI:0.49-0.84) and non-viral aHCC (HR: 0.56; 95%CI:0.40-0.79). While no baseline factor was predictive of a differential OS benefit with ramucirumab, analyzes demonstrated an association between high drug exposure, treatment-emergent hypertension (Grade {greater than or equal to}3) and increased ramucirumab benefit.
Ramucirumab provided a survival benefit irrespective of baseline prognostic covariates, and this benefit was greatest in patients with high ramucirumab drug exposure and/or those with treatment-related hypertension.