A Phase II, Open-Label Study of Ramucirumab in Combination with Paclitaxel and Carboplatin as First-Line Therapy in Patients with Stage IIIB/IV Non–Small-Cell Lung Cancer

INTRODUCTION: The objective of this study was to determine whether the addition of ramucirumab to first-line paclitaxel–carboplatin chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) resulted in a 6-month progression-free survival (PFS) rate that compares favorably with the historic rate for bevacizumab combined with paclitaxel–carboplatin in this patient population. METHODS: In this phase II, single-arm, open-label, multicenter study, 40 patients with advanced NSCLC received ramucirumab (10 mg/kg intravenous [IV]) followed by paclitaxel (200 mg/m(2) IV) and carboplatin area under the curve = 6 on day 1 every 21 days as first-line therapy. Therapy continued for up to six cycles. Patients not experiencing withdrawal criteria may have continued ramucirumab monotherapy every 3 weeks. The primary endpoint was PFS at 6 months, with 80% power to detect a 6-month PFS rate of at least 55%. RESULTS: The 6-month PFS rate was 59.0% and the objective response rate was 55.0%. The most common treatment-related adverse events were fatigue, peripheral neuropathy, nausea, epistaxis, and myalgia. Single-nucleotide polymorphism (SNP) rs2981582 on the FGFR-2gene had significant associations with improved overall survival, PFS, and best overall response (p values without multiplicity adjustment were 0.0059, 0.0429, and 0.0392, respectively). CONCLUSION: Ramucirumab in combination with paclitaxel–carboplatin resulted in a 6-month PFS rate and safety profile that compared favorably with the historical control. In addition, no deaths were associated with this treatment. Furthermore, we describe an association of SNP on FGFR-2 gene with survival and response. These findings warrant further clinical investigation in patients with NSCLC.