Exposure-response (E-R) and case-control analyses of ramucirumab leading to recommendation for dosing optimization in patients with gastric cancer.

2578 Background: Ramucirumab was approved for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma in combination with paclitaxel based on an efficacy and safety trial that demonstrated 2.2 months (median) of overall survival (OS) benefit with a hazard ratio of 0.81 (p = 0.02) for patients treated with ramucirumab plus paclitaxel as compared to patients treated with placebo plus paclitaxel. In exploratory Kaplan-Meier survival analyses stratified by model predicted ramucirumab minimum concentration after first dose (Cmin,1), the OS effect was only shown for the patients with Cmin,1 greater than the median value. Further exploratory E-R analyses were conducted. Methods: Data for E-R analyses were obtained from a randomized (1:1), double-blind, placebo-controlled, efficacy and safety trial that randomized 665 patients. Case-control analysis was conducted to match patients in the placebo arm to patients in each Cmin,1 quartile subgroup (Q1-Q4) based on key baseline prognostic factor...