Effect of common medications on immune checkpoint inhibitor efficacy.

Abstract

e14710 Background: Previous studies have suggested that certain common medications could impact immune checkpoint inhibitor (ICI) efficacy and survival. These studies lacked non-ICI control groups, raising the possibility that survival differences could be explained by confounding. Methods: We developed a pan-cancer cohort of 27,998 patients who received ICIs in the national Veterans Health Administration (VHA) from 2010 to 2023. ICI patients were matched to 66,488 historical control patients treated with chemotherapy or targeted therapy before initial ICI regulatory approval in each cancer. We ascertained baseline use of drugs from 15 common medication classes within 1 year before therapy start and performed propensity-weighted Cox regression analyses to assess the impact of each medication class on overall survival (OS) and time to next treatment (TTNT). Interaction tests measured whether the impact of each medication class was significantly different in ICI versus historical control patients. Results: In the ICI cohort, the most common cancer types were NSCLC (46%) and melanoma (10%). After adjustment for multiple comparisons, only statins (adjusted hazard ratio [aHR] 0.93), PPIs (aHR 1.06), and loop diuretics (aHR 1.19) were associated with overall survival differences among ICI patients; nearly identical associations were observed in historical control patients (interaction p-values > 0.4 for all; Table). Similar results were seen for TTNT and in sensitivity analyses limiting to more recent medication users. Conclusions: Common medications do not appear to impact ICI efficacy. Previously described survival effects are likely the result of confounding. [Table: see text]