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.