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
Edward B. Garon, Byoung Chul Cho, Alexander Luft, Jorge Alatorre-Alexander, Sarayut Lucien Geater, Dmytro Trukhin, Sang‐We Kim, Grygorii Ursol, Maen Hussein, Farah Louise Lim, Cheng‐Ta Yang, Luiz H. Araujo, Haruhiro Saito, Niels Reinmuth, Milena Kohlmann, Caitlin D. Lowery, Helen Mann, Solange Peters, Tony Mok, Melissa L. Johnson
Abstract
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.