758P - Ramucirumab in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha fetoprotein (AFP): An exposure-response analysis

REACH (NCT01140347) and REACH-2 (NCT02435433) studied ramucirumab (RAM) 8mg/kg Q2W in patients with HCC after sorafenib, with REACH-2 only enrolling patients with baseline AFP ≥400ng/mL. In REACH-2 RAM treatment improved overall survival (OS) compared to placebo (P), consistent with REACH (AFP ≥400ng/mL) patients. Here we describe exposure–response analyses (efficacy and safety) in patients from the studies. Individual patient data from patients with Child–Pugh A, BCLC stage B/C, and AFP ≥400ng/mL were pooled for exposure–response analyses (n=311 RAM with evaluable RAM exposure vs n=216 P). Estimates of exposure (minimum concentration after first dose [Cmin,1]) were treated as either continuous or categorical (group to quartiles) to evaluate the relationship to OS, progression-free survival (PFS), and as categorical to evaluate the relationship to selected safety endpoints. Multivariate Cox regression or case-matched control analysis was used to evaluate OS/PFS and adjust potential imbalance in baseline prognostic factors between each quartile and the P groups. Several poor prognostic factors, including Child–Pugh A6 and macrovascular invasion, appeared to be more frequent in the lower exposure quartiles. Increasing RAM exposure was significantly associated with improved OS (p