Treatment outcomes by histology in REVEL: A randomized phase III trial of Ramucirumab plus docetaxel for advanced non-small cell lung cancer

Objectives Ramucirumab, a recombinant human immunoglobulin G1 monoclonal antibody inhibiting vascular endothelial growth factor receptor-2, increased overall survival (OS) combined with docetaxel versus docetaxel alone in non-small cell lung cancer (NSCLC) in the REVEL trial. Pre-specified exploratory analysis examined efficacy and safety by histology. Materials and methods 1253 patients with NSCLC were randomized to receive ramucirumab (10 mg/kg; n = 628) plus docetaxel (75 mg/m2) or placebo plus docetaxel (n = 625) after disease progression on or after platinum-based therapy, with or without bevacizumab or maintenance therapy. OS was analyzed using Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using an unstratified Cox proportional hazards model. Primary quality-of-life analysis was time to deterioration (TtD) of the Lung Cancer Symptom Scale (LCSS) scores using the Kaplan-Meier method and Cox regression. Results Median OS for adenocarcinoma was 11.2 months for ramucirumab-docetaxel (n = 377) and 9.8 months for placebo-docetaxel (n = 348); HR = 0.83 (95% CI: 0.69–0.99). In squamous disease, median OS was 9.5 months for ramucirumab-docetaxel (n = 157) versus 8.2 months for placebo-docetaxel (n = 171); HR 0.88 (95% CI: 0.69–1.13). Median OS for other nonsquamous was 10.8 months for ramucirumab-docetaxel (n = 74) and 9.3 months for placebo-docetaxel (n = 78); HR = 0.86 (95% CI: 0.59–1.26). Treatment-emergent adverse events were comparable between treatment arms across histologic subgroups. TtD for LCSS scores was similar between treatment arms in the nonsquamous and squamous subgroups. Conclusion REVEL demonstrated similar favorable efficacy and manageable safety for ramucirumab-docetaxel across histologic subgroups of NSCLC.