Efficacy and safety of ramucirumab (RAM) for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma across age subgroups in two global phase 3 trials.

Abstract

3 Background: REGARD and RAINBOW are two phase 3 studies which demonstrated significant survival benefits and manageable toxicity in patients with advanced gastric cancer (GC) randomized in the second-line setting to receive RAM or placebo. We examined outcomes by age (≤45, 45-70, ≥70, ≥75 years). Methods: Patients were randomized 2:1 to receive RAM 8 mg/kg + best-supportive care (BSC) or placebo (PL) + BSC (REGARD); or 1:1 RAM 8 mg/kg + paclitaxel (PTX) or PL + PTX (RAINBOW). Kaplan-Meier analysis and Cox proportional hazards regression were performed for overall survival (OS) and progression-free survival (PFS). Subpopulation treatment effect pattern plot (STEPP) assessed efficacy and the incidence of adverse events (AEs) across age subgroups. Results: Baseline characteristics were generally well balanced between arms amongst the age subgroups. Efficacy outcomes are summarized in the Table. STEPP analysis revealed no obvious patterns for differential risks in terms of efficacy and AEs (any grade or grade ≥3) according to age. Conclusions: Compared with PL, the efficacy of RAM was maintained in all age groups, with similar rates of toxicity. Despite some limitations regarding patient numbers in some age subgroups, this exploratory subgroup analysis supports the use of RAM for the treatment of GC, irrespective of age. Clinical trial information: NCT00917384 and NCT01170663. [Table: see text]