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

Introduction:We report the primary analysis from JAVELIN Lung 100, a phase 3 trial comparing avelumab (anti -PD-L1) vs platinum-based doublet chemotherapy as first-line treatment for PD-L1+ advanced non-small cell lung cancer (NSCLC).Methods: Adults with PD-L1+ (≥1% of tumor cells; PD-L1 IHC 73-10 pharmDx), EGFR/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 endpoints 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: 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) vs chemotherapy (n=216) were 0.85 ([95% CI, 0.67-1.09];1-sided p=0.1032; median OS, 20.1 vs 14.9 months), and 0.71 ([95% CI, 0.54-0.93];1-sided p=0.0070; median PFS, 8.4 vs 5.6 months), respectively.With avelumab QW (n=130) vs chemotherapy (n=129), HRs were 0.79 ([95% CI, 0.59-1.07];1-sided p=0.0630; median OS, 19.3 vs 15.3 months) and 0.72 ([95% CI, 0.52-0.98];1-sided p=0.0196; median PFS, 7.5 vs 5.6 months), respectively.No new safety signals were observed.Conclusions: Longer median OS and PFS were observed with avelumab vs 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