Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1–Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial
Martin Reck, Fabrice Barlési, James C. Yang, Virginie Westeel, Enriqueta Felip, Mustafa Özgüroğlu, Manuel Cobo, Richard Sullivan, Dariusz M. Kowalski, Zoran Andrić, Dae Ho Lee, Ahmet Sezer, Ping Hu, XiaoZhe Wang, Anja von Heydebreck, Natalia Jacob, Keyvan Tadjalli Mehr, Keunchil Park
Abstract
INTRODUCTION: We report the primary analysis from JAVELIN Lung 100, a phase 3 trial comparing avelumab (anti-programmed death-ligand 1 [PD-L1]) versus platinum-based doublet chemotherapy as first-line treatment for PD-L1-positive (+) advanced NSCLC. METHODS: Adults with PD-L1+ (≥1% of tumor cells; PD-L1 immunohistochemistry 73-10 pharmDx), EGFR and ALK wild-type, previously untreated, stage IV NSCLC were randomized to avelumab 10 mg/kg every 2 weeks (Q2W), avelumab 10 mg/kg once weekly (QW) for 12 weeks and Q2W thereafter, or platinum-based doublet chemotherapy every 3 weeks. Primary end points were overall survival (OS) and progression-free survival (PFS) per independent review committee. The primary analysis population was patients with high-expression PD-L1+ tumors (≥80% of tumor cells). RESULTS: A total of 1214 patients were randomized to avelumab Q2W (n = 366), avelumab QW (n = 322), or chemotherapy (n = 526). In the primary analysis population, hazard ratios (HRs) for OS and PFS with avelumab Q2W (n = 151) versus chemotherapy (n = 216) were 0.85 (95% confidence interval [CI]: 0.67-1.09; one-sided p = 0.1032; median OS, 20.1 versus 14.9 mo) and 0.71 (95% CI: 0.54-0.93; one-sided p = 0.0070; median PFS, 8.4 versus 5.6 mo), respectively. With avelumab QW (n = 130) versus chemotherapy (n = 129), HRs were 0.79 (95% CI: 0.59-1.07; one-sided p = 0.0630; median OS, 19.3 versus 15.3 mo) and 0.72 (95% CI: 0.52-0.98; one-sided p = 0.0196; median PFS, 7.5 versus 5.6 mo), respectively. No new safety signals were observed. CONCLUSIONS: Longer median OS and PFS were observed with avelumab versus platinum-based doublet chemotherapy in advanced NSCLC, but differences in OS and PFS were not statistically significant, and the trial did not meet its primary objective. CLINICALTRIALS: gov Identifier: NCT02576574.