Predictive factors for the efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer: a retrospective study.

BACKGROUND: Randomized clinical studies have demonstrated that programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can provide significant survival benefit to patients with advanced non-small cell lung cancer (NSCLC). However, the real-world application of inhibitors is complex, necessitating a comprehensive summary of their efficacy and adverse effects. Our study is specifically designed to reach this objective. METHODS: We retrospectively analyzed the efficacy and immune-related adverse events (irAEs) in patients with locally advanced or stage IV NSCLC who received PD-1/PD-L1 inhibitors as monotherapy or in combination with other antitumor drugs at a single center. RESULTS: Among 123 patients, the median progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were 24.0 weeks, 42.3%, and 66.7%, respectively. Multivariate analysis identified Eastern Cooperative Oncology Group performance status (ECOG PS) 2-3, irAEs occurrence, tumor cell proportion score (TPS) ≥50%, and non-Kirsten rat sarcoma (KRAS) driver gene alterations as factors significantly associated with PFS. Landmark analysis was conducted to minimize immortal time bias and revealed the association of irAEs with efficacy. Of the patients, 39.8% experienced irAEs, with skin-related irAEs being the most common (22.0%), followed by thyroid dysfunction (13.0%) and pneumonia (12.2%). Approximately 16.3% of patients temporarily or permanently discontinued immunotherapy due to irAEs. No deaths were attributed to irAEs. CONCLUSIONS: Real-world data on the efficacy and safety of PD-1/PD-L1 inhibitors in patients with advanced NSCLC were generally consistent with results from randomized clinical trials. ECOG PS 2-3, non-KRAS driver gene alterations, TPS ≥50%, and irAEs were found to be significantly associated with PFS. Landmark analysis further demonstrated that the occurrence of irAEs was correlated with better efficacy of immunotherapy.