1341P - Exploring the role of the gut microbiome on the efficacy of ipilimumab and nivolumab in advanced non-small cell lung cancer: A prospective observational study

Background

The combination of ipilimumab and nivolumab has shown promising outcomes in advanced non-small cell lung cancer (NSCLC), even with low PD-L1 levels. Identifying predictive biomarkers and deciding whether to add chemotherapy to the ipilimumab and nivolumab regimen remains challenging. The gut microbiome has emerged as a significant influencer of immunotherapy efficacy, with dysbiosis from antibiotics or proton pump inhibitors (PPIs) use reducing the success of immunotherapy.

Methods

From April 2021 to September 2023, 50 NSCLC patients scheduled for ipilimumab and nivolumab with or without chemotherapy were enrolled. Fecal samples collected before treatment were analyzed using 16S rRNA sequencing to assess the gut microbiome. This study prospectively evaluated the impact of antibiotic or PPI usage and the pre-treatment gut microbiome on the efficacy of the ipilimumab and nivolumab combination therapy.

Results

The entire cohort had a median progression-free survival (PFS) of 5.6 months and a median overall survival (OS) of 11.9 months. Pre-treatment antibiotic use was significantly associated with shorter PFS (2.8 months vs. 9.5 months, p=0.04). Analysis showed enrichment of Gemella and Catenibacterium in patients with a history of antibiotic use, while Bifidobacterium enriched in those without. Additionally, gut microbiome diversity significantly correlated with PFS in the ipilimumab and nivolumab group, but not in the group receiving both ipilimumab, nivolumab, and chemotherapy.

Conclusions

Pre-treatment antibiotic use potentially induces dysbiosis, increasing gut bacteria like Gemella and Catenibacterium that may impair the efficacy of ipilimumab and nivolumab. Furthermore, the diversity of the pre-treatment gut microbiome could serve as a novel criterion for deciding on the addition of chemotherapy to the ipilimumab and nivolumab. These insights offer potential advances toward personalized medicine in NSCLC treatment, suggesting that gut microbiome profiling could guide therapeutic decisions and improve outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Yamada, T. Kohichi: Financial Interests, Personal, Research Grant: Ono Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.