A Brief Report of Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: Outcomes by Tumor PD-L1 Expression in the Phase 3 POSEIDON Study

IntroductionIn the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and platinum-based chemotherapy (T+D+CT) significantly improved overall survival (OS; hazard ratio HR 0. 77 95% confidence interval CI 0. 65–0. 92; P=. 0030) and progression-free survival (PFS) versus chemotherapy alone (CT) in patients with metastatic NSCLC (mNSCLC), leading to approval for this regimen. We report outcomes by programmed cell death ligand-1 (PD-L1) tumor cell (TC) expression level. MethodsPatients with EGFR/ALK wild-type mNSCLC were randomized (1: 1: 1) to T+D+CT, durvalumab plus chemotherapy (D+CT), or CT with stratification by PD-L1 expression (TC ≥50% vs <50%), disease stage, and histology. In this post-hoc exploratory analysis, OS, PFS, objective response rate, duration of response, and safety were assessed in subgroups with PD-L1 TC ≥1% versus <1%. ResultsAmong 1012/1013 randomized patients with known PD-L1 status, 644 (63. 6%) versus 368 (36. 4%) had TC ≥1% versus <1%. T+D+CT numerically improved (HR 95% CI) OS (TC ≥1%, 0. 76 0. 61–0. 95; <1%, 0. 77 0. 58–1. 00) and PFS (TC ≥1%, 0. 68 0. 54–0. 85; <1%, 0. 78 0. 59–1. 03) versus CT in both subgroups. D+CT showed numerical OS improvement versus CT in the TC ≥1% subgroup (0. 79 0. 64–0. 98) but not the <1% subgroup (0. 99 0. 76–1. 30), with similar PFS results. Safety in both subgroups was consistent with the overall population. ConclusionsThis exploratory analysis supports T+D+CT as a first-line treatment option for patients with mNSCLC irrespective of PD-L1 expression, including the harder-to-treat subgroup with PD-L1 TC <1%, consistent with the role of cytotoxic T-lymphocyte-associated antigen 4 and PD-L1 in the immune response.