Lack of impact of antibiotics and proton pump inhibitors on the efficacy of preoperative chemoimmunotherapy in locally advanced non-small cell lung cancer: A multicenter retrospective study.

[INTRODUCTION] Antibiotics and proton pump inhibitors (PPIs) have been associated with the reduced efficacy of immune checkpoint inhibitor (ICI) in patients with advanced non-small cell lung cancer (NSCLC). This study assessed the clinical impact of these medications in the neoadjuvant setting.

[PATIENTS AND METHODS] This multicenter retrospective study was conducted in 29 Japanese institutions. Between March 2023 and July 2024, 131 patients with resectable clinical stage II-III NSCLC who received neoadjuvant chemoimmunotherapy with nivolumab were enrolled. In total, 113 patients who underwent definitive surgery were included in the surgical outcome analysis. We investigated the association between the use of antibiotics and PPIs within 30 days before treatment initiation and clinicopathological factors, including the pathological complete response (pCR) and major pathological response (MPR).

[RESULTS] Among 113 patients, 5 (4.4%) had received antibiotics and 23 (20.4%) PPIs. Antibiotic and PPI use showed no significant differences in any clinicopathological factors. Antibiotic and PPI use was not significantly associated with the objective response rate (ORR), pCR, or MPR; antibiotic (use/non-use): 80.0%/70.4% (p = 1.000), 40.0%/35.8% (p = 1.000), 60.0%/59.6% (p = 1.000) and PPI (use/non-use): 78.3%/68.9% (p = 0.532), 43.5%/33.3% (p = 0.507), 60.9%/58.9% (p = 1.000).

[CONCLUSION] Prior use of antibiotics and PPIs was not significantly associated with radiological or pathological response of neoadjuvant ICI in patients with resectable NSCLC. Further studies with larger sample size and longer survival follow-up are needed.