Clinical impact of probiotics on the efficacy of <scp>anti‐PD</scp>‐1 monotherapy in patients with nonsmall cell lung cancer: A multicenter retrospective survival analysis study with inverse probability of treatment weighting
Kazuki Takada, Mototsugu Shimokawa, Shinkichi Takamori, Shinichiro Shimamatsu, Fumihiko Hirai, Tetsuzo Tagawa, Tatsuro Okamoto, Motoharu Hamatake, Yuko Tsuchiya‐Kawano, Kohei Otsubo, Koji Inoue, Yasuto Yoneshima, Kentaro Tanaka, Isamu Okamoto, Yoichi Nakanishi, Masaki Mori
Abstract
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 nonsmall cell lung cancer (NSCLC) is poorly understood. The outcomes of 294 patients with advanced or recurrent NSCLC who received antiprogrammed cell death-1 (PD-1) therapy (nivolumab or pembrolizumab monotherapy) at three medical centers in Japan were analyzed in our 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 (nonuse vs use: hazard ratio [HR] [95% confidence interval {CI}] = 1.73 [1.42-2.11], log-rank test P = .0229), but not overall survival (nonuse vs use: HR [95%CI] = 1.40 [1.13-1.74], log-rank test P = .1835), was significantly longer in patients who received probiotics. Moreover, the IPTW-adjusted univariate analyses showed that nonuse or use of probiotics was significantly associated with disease control (nonuse vs use: odds ratio [OR] [95%CI] = 0.51 [0.35-0.74], P = .0004) and overall response (nonuse vs use: OR [95%CI] = 0.43 [0.29-0.63], P < .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.