Effect of post-discontinuation therapy (PDT) on survival in metastatic gastric-gastroesophageal junction (G-GEJ) adenocarcinoma patients from the RAINFALL trial: An exploratory analysis.

Background: The global, randomized, placebo (PL)-controlled phase 3 RAINFALL trial evaluated if addition of ramucirumab (RAM) to first-line (1L) cisplatin plus fluoropyrimidine (chemo) improved survival. Imbalances in PDT (including cross over) could confound OS analysis comparison of 1L therapies. We report the PFS & OS, as previously disclosed at ASCO-GI 2018, and investigated the impact of PDT on survival in a post-hoc analysis. Methods: Study blinding was continued until final OS data-lock. Investigators could choose any treatment for PDT. To compare OS from randomization as well as from the start of second-line (2L) treatment (Landmark OS), PDT were categorized into RAM or Non-RAM containing, RAM+paclitaxel(PTX), or All Others. Analyses were stratified by ECOG PS, primary tumor location, disease measurability & geographic region. Results: 326 pts were randomized to chemo+RAM (8 mg/kg iv D1, D8, every 21d) & 319 pts to chemo+PL (ITT, N= 645). The primary endpoint of investigator-assessed PFS was met (HR, 0.75; 95% CI 0.61-0.94; p = 0.011; median, 5.7 vs 5.4 mo) while no OS benefit was observed (HR, 0.96; 95% CI 0.80-1.16; p = 0.68; median, 11.2 vs 10.7 mo). 150 pts (46%) in the RAM arm received PDT compared to 164 (51%) in the PL arm. Subgroup results are summarized in Table. Conclusions: PDT use was balanced in both arms. OS from Randomization and Landmark OS is numerically higher in patients who received RAM containing PDT compared to Non-RAM PDT. Despite the small sample size, the results are consistent with previously demonstrated OS benefit with RAM+PTX as 2L therapy. (Table Presented).