Impact of immune-related adverse event severity on overall survival in patients with advanced NSCLC receiving immune checkpoint inhibitors therapy, with a focus on combination regimens

BACKGROUND: Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) may serve as prognostic markers in non-small cell lung cancer (NSCLC). While prior studies suggest differences in overall survival (OS) based on irAE, their prognostic impact across various ICI regimens remains underexplored. METHODS: This retrospective study analyzed data from patients with advanced or recurrent NSCLC treated with ICIs between January 2018 and December 2022. Patients were categorized into three groups: severe irAEs (Grade 3-5), mild irAEs (Grade 1-2), and no-irAEs. OS was assessed across three regimens: anti-programmed cell death protein 1 (anti-PD-1) monotherapy, anti-PD-1/anti-programmed death-ligand 1 (anti-PD-L1) with chemotherapy (CT), and anti-PD-1 with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) ± CT. RESULTS: Among the 256 patients included, 55 received anti-PD-1 monotherapy, 116 received anti-PD-1/L1 with CT, and 85 received anti-PD-1 with anti-CTLA-4 ± CT. For anti-PD-1 monotherapy, median OS (95 % confidence interval) was 38.3 (17.0-42.5) months in the mild irAE group, 16.1 (5.2-28.6) months in the severe irAE group, and 9.6 (12.3-37.1) months in the no-irAE group. In the anti-PD-1/L1 with CT group, median OS were 33.6 (14.2-40.3), 16.0 (1.84-not reached [NR]), and 17.7 (3.8-23.4) months, respectively. For anti-PD-1 with anti-CTLA-4 ± CT, median OS were 28.0 (21.8-NR), 10.9 (7.0-19.6), and 16.3 (8.7-23.4) months, respectively. CONCLUSIONS: The relationship between irAE severity and OS was consistent across all ICI regimens, with patients experiencing mild irAEs demonstrating better OS across all ICI regimens.