Background: Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m2 paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure–response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial. Methods: Using sparse pharmacokinetic samples collected in the RAINBOW trial, a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (Cmin,ss) using a nonlinear mixed-effect modeling approach. Kaplan–Meier and Cox proportional hazards analyses were conducted to evaluate ramucirumab exposure (Cmin,ss) and efficacy relationship by overall survival and progression-free survival. Exposure-safety relationships were assessed descriptively. Results: Two hundred and twenty-two East Asian patients were included in this exposure–response analysis. Higher ramucirumab Cmin,ss was associated with longer overall survival (p = 0.0115) and progression-free survival (p = 0.0179) in this patient cohort. Patients with higher ramucirumab Cmin,ss (≥56.87 ng/ml median) had higher incidences of grade ≥3 leukopenia and neutropenia, but not febrile neutropenia or hypertension. Conclusions: This exploratory analysis suggests a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in East Asian patients from RAINBOW, consistent with the overall exposure–response analysis from this trial. A regimen with a higher dosage of ramucirumab warrants further consideration for East Asian patients with gastric/GEJ cancer.
All Science Journal Classification (ASJC) codes
- Cancer Research