Effect of the Combination of Concomitant Drugs on Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung...

Emerging evidence indicates that baseline use of certain concomitant drugs may affect the efficacy of immune checkpoint inhibitors (ICIs), including PD-1, PD-L1, and CTLA-4 inhibitors, in patients with cancer. However, most previous studies have evaluated individual drug classes in isolation, without considering potential interactions among multiple drugs.

This study aimed to evaluate the individual and combined effects of commonly prescribed concomitant drugs on the efficacy and safety of ICI-based therapy in patients with non-small cell lung cancer (NSCLC).

We conducted a retrospective analysis of 124 patients with advanced or recurrent NSCLC who received first-line ICI-based treatments at a single institution. Drug exposure at treatment initiation was assessed for proton pump inhibitors (PPIs), low-dose aspirin, non-steroidal anti-inflammatory drugs, statins, biguanides, antibiotics, and probiotics. Associations with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were analyzed using multivariate Cox regression models.

PPI use was independently associated with shorter PFS (HR: 2.44, p < 0.001) and OS (HR: 2.04, p = 0.01). In contrast, low-dose aspirin use was independently associated with longer PFS (HR: 0.31, p = 0.01). Patients receiving both PPIs and aspirin had longer PFS and OS compared to those receiving PPIs alone, although the differences were not statistically significant. No consistent associations were observed for other drugs. The incidence of irAEs was not significantly affected by concomitant drug use.

PPI use at baseline may be associated with reduced efficacy of ICI therapy in NSCLC patients. In contrast, low-dose aspirin use was independently associated with improved PFS, and may potentially mitigate the negative effects of PPIs. These findings underscore the importance of considering concomitant drug use when initiating ICI treatment. Prospective studies are needed to validate these observations and clarify underlying mechanisms.