Association of IClostridium butyricum/I Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations

• Published in: Cancers 2023-12, Vol.16 (1)
• Main Authors: Tomita, Yusuke, Sakata, Shinya, Imamura, Kosuke, Iyama, Shinji, Jodai, Takayuki, Saruwatari, Koichi, Hamada, Shohei, Akaike, Kimitaka, Anai, Moriyasu, Fukusima, Kazuaki, Takaki, Akira, Tsukamoto, Hirotake, Goto, Yoshihiko, Motozono, Chihiro, Sugata, Kenji, Satou, Yorifumi, Ueno, Takamasa, Ikeda, Tokunori, Sakagami, Takuro
• Format: Article
• Language: English
• Subjects: Cancer; Cancer patients; Care and treatment; Cell death; Immunotherapy; Ipilimumab; Lung cancer, Non-small cell; Metastasis; Microbiota (Symbiotic organisms); Patient outcomes; Pemetrexed
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16010047

Gut microbiota is a key regulators of the efficacy of immune checkpoint inhibitor (ICIs). Thus, manipulating microbiota may enhance cancer treatment outcomes. Clostridium butyricum MIYAIRI 588 strain (CBM588) enhances the effects of ICI monotherapy in patients with advanced lung cancer. However, its effect on the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We retrospectively analyzed 106 patients with stage IV or recurrent metastatic non-small cell lung cancer (NSCLC) consecutively treated with chemoimmunotherapy combination. CBM588 significantly extended the overall survival in patients with NSCLC receiving chemoimmunotherapy combinations and was associated with overall survival in patients using proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of commensal microbiota has the potential to enhance the efficacy of chemoimmunotherapy combinations. The survival benefit of CBM588 in the tumor-programmed cell death ligand 1 (PD-L1) < 1% cohort was higher than that in the PD-L1 1–49% and PD-L1 ≥ 50% cohorts. Further exploration of the synergy between CBM588 and immunotherapy is warranted. The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients received Clostridium butyricum therapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on th