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

Introduction In 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. Methods Patients 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%. Results Among 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. Conclusions This 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.