Effects of Concomitant Medications on the Therapeutic Effectiveness of PD-1/PD-L1 Inhibitors in Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study

Background: Patients with advanced non-small cell lung cancer (NSCLC) often require concurrent administration of other medications during immunotherapy to manage cancer-related complications or symptoms. However, these concomitant medications may interact with immune checkpoint inhibitors (ICIs), potentially impacting their therapeutic effectiveness. Aim: The study aims to systematically investigate the effect of concomitant medications for anti-tumor effectiveness of PD-1/PD-L1 inhibitors, providing suggestions for the selection of concomitant medications during ICIs treatment in NSCLC patients. Methods: This retrospective study collected and analyzed clinical characteristics and concomitant medication information of 650 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors at Xiangya Hospital. The impact of commonly used concomitant medications on patients' progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) was analyzed using SPSS 28.0. Propensity score matching (PSM) was employed to mitigate the influence of other confounding factors. The Log-rank test and Cox proportional hazards model were used to identify independent predictors of PFS. Results: Univariate COX analysis showed that antimicrobial agents, proton pump inhibitors (PPIs), calcium channel blockers (CCBs), glucocorticoids (GCs), non-steroidal anti-inflammatory drugs (NASIDs), antihistamines, anticoagulants, and opioids reduced PFS and lowered ORR and DCR ( P <0.01), while antihypertensive drugs (excluding CCBs), sedative-hypnotics, antidiabetic drugs, statins, and bronchodilators had no effect on antitumor efficacy. Additionally, the use of aspirin is significantly correlated with better PFS, ORR, and DCR ( P <0.05). Moreover, Multivariate Cox regression analysis indicated that the use of antimicrobial agents, PPIs, GCs and opioids are independent risk factors that adversely affect the effectiveness of PD-1/PD-L1 inhibitor therapy ( P <0.001). After PSM, their use remained linked to worse PFS, ORR, and DCR. Conclusion: Concomitant use of antimicrobial agents, PPIs, GCs, and opioids may diminish the antitumor efficacy of PD-1/PD-L1 inhibitors. Therefore, clinicians should consider these factors before prescribing ICIs to patients with NSCLC.