Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes from the Phase 3 POSEIDON Trial.
Solange Peters, Byoung Chul Cho, Alexander V Luft, Jorge Alatorre-Alexander, Sarayut Lucien Geater, Konstantin Laktionov, Dmytro Trukhin, Sang-We Kim, Grygorii M Ursol, Maen Hussein, Farah Louise Lim, Cheng-Ta Yang, Luiz Henrique Araujo, Haruhiro Saito, Niels Reinmuth, Caitlin Lowery, Helen Mann, Ross Stewart, Haiyi Jiang, Edward B Garon, Tony Mok, Melissa L Johnson
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引用次数: 0
Abstract
Introduction: The primary analysis (median follow-up 34.9 months across all arms) of the phase 3 POSEIDON study demonstrated a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR/ALK-wild-type metastatic NSCLC (mNSCLC). D+CT showed a trend for OS improvement versus CT that did not reach statistical significance. This paper reports prespecified OS analyses after longer-term follow-up (median >5 years).
Methods: 1013 patients were randomized (1:1:1) to T+D+CT, D+CT, or CT, stratified by tumor cell (TC) PD-L1 expression (≥50% vs <50%), disease stage (IVA vs IVB), and histology (squamous vs nonsquamous). Serious adverse events were collected during follow-up.
Results: After median follow-up of 63.4 months across all arms, T+D+CT showed sustained OS benefit versus CT (hazard ratio [HR] 0.76, 95% CI: 0.64-0.89; 5-year OS: 15.7% vs 6.8%). OS improvement with D+CT versus CT (HR 0.84, 95% CI: 0.72-1.00; 5-year OS: 13.0%) was consistent with the primary analysis. OS benefit with T+D+CT versus CT remained more pronounced in nonsquamous (HR 0.69, 95% CI: 0.56-0.85) versus squamous (HR 0.85, 95% CI: 0.65-1.10) mNSCLC. OS benefit with T+D+CT versus CT was still evident regardless of PD-L1 expression, including patients with PD-L1 TC <1%, and remained evident in STK11-mutant (nonsquamous), KEAP1-mutant, and KRAS-mutant (nonsquamous) mNSCLC. No new safety signals were identified.
Conclusions: After median follow-up of >5 years, T+D+CT showed durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease.
期刊介绍:
Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.