Clinical impact of probiotics on the efficacy of anti-PD-1 monotherapy in patients with non-small cell lung cancer: A multicenter retrospective survival analysis study with inverse probability of treatment weighting

The gastrointestinal microbiota was reported as an important factor for the response to cancer immunotherapy. Probiotics associated with gastrointestinal dysbiosis and bacterial richness may affect the efficacy of cancer immunotherapy drugs. However, the clinical impact of probiotics on the efficacy of cancer immunotherapy in patients with non-small cell lung cancer (NSCLC) is poorly understood. The outcomes of 294 patients with advanced or recurrent NSCLC who received anti-programmed cell death-1 (PD-1) therapy (nivolumab or pembrolizumab monotherapy) at three medical centers in Japan were analyzed in this study. We used inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds. The IPTW-adjusted Kaplan-Meier curves showed that progression-free survival (non-use vs. use: hazard ratio [HR] [95% confidence interval {CI}] = 1.73 [1.42-2.11], log-rank test P = 0.0229), but not overall survival (non-use vs. use: HR [95%CI] = 1.40 [1.13-1.74], log-rank test P = 0.1835), was significantly longer in patients who received probiotics. Moreover, the IPTW-adjusted univariate analyses showed that non-use or use of probiotics was significantly associated with disease control (non-use vs. use: odds ratio [OR] [95%CI] = 0.51 [0.35-0.74], P = 0.0004) and overall response (non-use vs. use: OR [95%CI] = 0.43 [0.29-0.63], P < 0.0001). In this multicenter and retrospective study, probiotics use was associated with favorable clinical outcomes in patients with advanced or recurrent NSCLC who received anti-PD-1 monotherapy. The findings should be validated in a future prospective study. This article is protected by copyright. All rights reserved.