Docetaxel plus Ramucirumab vs Docetaxel plus Placebo as Second-line Treatment for Advanced NSCLC: a Phase 2 Multicenter Trial in Japan
Ramicirumab (RAM) is a human IgG1 monoclonal antibody that specifically binds to and inhibits vascular endothelial growth factor receptor-2 (VEGFR2).a A randomized global phase 3 trial (REVEL) demonstrated statistically significant improvement in overall survival (OS) and progression-free survival (PFS) for docetaxel plus ramucirumab (DR) versus docetaxel (DOC) as second line therapy in patients with advanced NSCLC.b This led to the approval of DR for this indication in December 2014. However, a limited number of East Asian patients were given DOC at 75 mg/m2 in REVEL, which may have an impact on the use of this combination in Japan. Hosomi and colleaguesc reported on a phase 2, randomized, double-blind, multicenter study conducted in Japan to evaluate the efficacy of DR for stage IV NSCLC following disease progression during or after platinum-based chemotherapy. Patients with EGFR-mutant stage IV NSCLC who received prior EGFR tyrosine kinase inhibitor (TKI) therapy were randomized 1:1 to receive DOC 60 mg/m2 plus ramucirumab 10 mg/kg IV (n=79) or DOC plus placebo (n=81) on Day 1 of a 21-day cycle until disease progression. The primary endpoint was PFS to be analyzed after observing 134 PFS events for patients without prior EGFR-TKI therapy. Secondary endpoints included safety profile, OS, objective response rate (ORR), disease control rate (DCR), and patient-reported outcomes.
The median PFS was 5.2 months (95% CI 3.52, 6.97) for DR and 4.2 months [2.83, 5.62] for DOC plus placebo (hazard ratio [HR] 0.83 [0.59, 1.16]). The ORR was 28.9% (DR) versus 18.5% (DOC+placebo), and the DCR was 78.9% (DR), 70.4% (DOC+placebo). The median OS at the time of primary PFS analysis was 15.2 months for DR and 14.0 months for DOC plus placebo. Main Grade 3/4 toxicities (DR vs DOC) were neutropenia (90% vs 86%), leukopenia (70% vs 68%), febrile neutropenia (33% vs 20%) and anorexia (7% vs 5%). The Grade 3/4 febrile neutropenia did not lead to any fatal events and the incidence of Grade ? 3 infections were 1% vs 10%. These efficacy results were consistent with those from REVEL in that DR showed clinical benefit over DOC in terms of PFS, ORR, and DCR in Japanese NSCLC patients. DR was well tolerated, with manageable low grade toxicity.
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- Hosomi Y, et al. ASCO 2015. Abstract 8054.