Factors influencing the selection of CheckMate-9LA (nivolumab, ipilimumab, and chemotherapy) regimen in AGA-negative advanced NSCLC.

Abstract

e20667 Background: The treatment of advanced non-small cell lung cancer (aNSCLC) without actionable genomic alteration (AGA) has seen significant improvement with the introduction of immunecheckpoint inhibitors. However, challenges persist in selecting the optimal first-line (1L) treatment regimen. This study aims to identify clinical, pathological, and non-clinical factors influencing the selection of the CheckMate 9LA (CM9LA) regimen (nivolumab and ipilimumab with chemotherapy) through a retrospective chart review and a brief clinician survey at a Canadian academic centre. Methods: This retrospective observational cohort study included adults with AGA-negative aNSCLC treated with the CM9LA regimen at a tertiary care centre between May 2020 and July 2025. Data were extracted from electronic medical records (EMRs), and a brief clinician survey assessed decision-making regarding CM9LA selection. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods, with exploratory stratified analyses and Univariate Cox regression to evaluate associations with baseline factors. Concordance between survey-derived decision-making themes and observed clinical characteristics was assessed descriptively. Statistical analyses were performed using IBM SPSS Statistics, and p-values < 0.05 were considered statistically significant. Results: Thirty-six patients with AGA-negative aNSCLC received 1L CM9LA. The median age at diagnosis was 66.5 years, with a male predominance (72%). Most patients (89%) had an ECOG status of 0-1, and > 90% had a history of smoking. Almost evenly split between adenocarcinoma (44%) and squamous cell carcinoma (39%), the majority (55.6%) were PD-L1 negative. Most patients (94%) had ≥ 2 visceral metastases, commonly in bone (39%) and brain (25%). Median follow-up was 20.2 months, with median PFS of 12.1 months and OS of 18.1 months. Worse outcomes were observed in patients with brain metastasis (p = 0.01) and squamous histology (p = 0.01), and were associated with lower albumin (p = 0.03), higher LDH (p = 0.03), and greater visceral metastatic burden (p = 0.02). Treatment preference documentation was present in 64% of cases and was not related to differences in survival. Clinician survey responses indicated that CM9LA selection was driven by perceived survival benefit, squamous histology, limited chemotherapy exposure, patient willingness and favourable fitness, with concordance between survey themes and real-world use in patients with good performance status, while PD-L1 expression was less decisive. Conclusions: The selection of CM9LA in real-world practice is influenced by patient fitness, disease burden, practical considerations, and clinician decision-making, with survey responses aligning with observed practice and outcomes, thereby supporting individualized treatment decisions.