The REVEL study was a randomized, double-blind, phase 3 study of docetaxel (DOC) plus ramucirumab (RAM; a human anti-VEGFR-2 monoclonal antibody) compared with DOC plus placebo (PBO) as second-line therapy for stage IV NSCLC following disease progression after prior platinum-based chemotherapy (Perol M, et al. ASCO 2014. Abstract LBA8006). In REVEL, 1253 patients with nonsquamous (NSQ; 74% of patients) and squamous (SQ; 26% of patients) stage IV NSCLC were randomized to receive DOC plus either RAM or PBO until disease progression, development of unacceptable toxicity, or death. The primary endpoint of the study was overall survival (OS), with secondary endpoints of progression-free survival (PFS) and overall response rate (ORR). The presentation at ASCO 2014 reported an ORR of 22.9% for RAM + DOC and 13.6% for PBO + DOC (P <.001). Median PFS was 4.5 months for RAM + DOC and 3.0 months for PBO + DOC. Importantly, OS was significantly improved in the group treated with RAM + DOC compared with those receiving PBO + DOC, with a hazard ratio of 0.857 (P = .0235). Median OS in the RAM + DOC group was 10.9 months versus 9.1 months in the PBO + DOC group, and this difference persisted for both NSQ and SQ histologies. Grade 3/4 adverse events that occurred at higher frequency in the RAM + DOC group included neutropenia, febrile neutropenia, fatigue, leukopenia, hypertension, and pneumonia. Grade 5 adverse events were comparable between arms. While REVEL demonstrated a statistically significant improvement in ORR, disease-free survival, and OS for RAM + DOC as second-line therapy in patients with stage IV NSCLC, the question remains regarding the value this regimen brings—how should oncologists balance the extra cost of RAM against an improvement of less than 2 months in median OS?
