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

Abstract

• In the phase 3 POSEIDON study, patients with EGFR/ALK wild-type metastatic NSCLC (mNSCLC) were randomized (1:1:1) to first-line tremelimumab plus durvalumab and platinum-based chemotherapy (T + D + CT), durvalumab plus chemotherapy (D + CT), or chemotherapy alone (CT), with stratification by programmed cell death ligand-1 (PD-L1) tumor cell (TC) expression level (≥ 50% vs. < 50%), disease stage, and histology. • In alpha-controlled analyses in the ITT population, T + D + CT significantly improved overall survival (OS) and progression-free survival (PFS) versus CT, leading to approval for this regimen. PFS was also significantly improved with D + CT versus CT; a trend for improved OS did not reach statistical significance. • Patients with PD-L1-low or -negative tumors may show primary resistance to anti-PD-(L)1 therapy, with real-world data suggesting that treatment benefits observed in trials do not always translate into optimal outcomes in clinical practice. • Here we report outcomes from POSEIDON from post-hoc exploratory analyses in subgroups with PD-L1 TC ≥ 1% versus < 1%. • Among 1012/1013 randomized patients with known PD-L1 status, 644 (63.6%) versus 368 (36.4%) had PD-L1 TC ≥ 1% versus < 1%. • Both T + D + CT and D + CT appeared to show OS/PFS benefit versus CT in patients with PD-L1 TC ≥ 1%. • Consistent with the role of cytotoxic T-lymphocyte-associated antigen 4 and PD-L1 in the immune response, the addition of tremelimumab to first-line durvalumab and chemotherapy also conferred clinical benefit to patients with PD-L1 TC < 1% mNSCLC. • This exploratory subgroup analysis of POSEIDON 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%. © 2024 The Authors