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Poster Display session 3

1310 - Association of SCFA in gut microbiome and clinical response in solid cancer patients treated with andi-PD-1 antibody.

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Presenters

Motoo Nomura

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

M. Nomura1, R. Nagatomo2, K. Inoue2, K. Doi1, J. Shimizu1, K. Baba1, T. Saito1, S. Matsumoto1, M. Muto1

Author affiliations

  • 1 Medical Oncology, Kyoto University Graduate School of Medicine, 606-8507 - Kyoto/JP
  • 2 Laboratory Of Clinical And Analytical Chemistry, Ritsumeikan University, 525-8577 - Kusatsu/JP

Resources

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Abstract 1310

Background

Although immunotherapy with immune checkpoint inhibitors (ICIs) has been remarkably effective across multiple cancer types. Several reports showed the gut microbiome is a possible factor proposed to impact the efficacy of ICI. The relationship between gut microbiome and immune status in tumor microenvironment remains unclear. Short-chain fatty acids (SCFAs) are major end products of gut microbiota metabolites and are known to wide-ranging impacts on host physiology. The objective of this study was to evaluate the fecal SCFA (fSCFA) in solid cancer patients treated with anti-programmed death-1 inhibitor (PD1i).

Methods

This was a prospective study of patients with cancer who were treated with nivolumab (2 mg/kg, every 3 weeks; 3 mg/kg, every 2 weeks; or 240 mg/body, every 2 weeks) or pembrolizumab (200 mg/body, every 3 weeks) at Kyoto University Hospital between July 2016 and April 2018. Patients were classified into two groups: responder (R) with an objective response and non-responder (NR) according to the Response Evaluation Criteria in Solid Tumors version 1.1. Fecal samples were collected before administration of PD-1 inhibitor and were analyzed by the ultra-high performance liquid chromatography-tandem mass spectrometry system.

Results

A total of 40 patients (melanoma 19; head and neck cancer 7; gastrointestinal cancer 7; genitourinary cancer 4; other 3) were enrolled. The response rate was 22.5%. The fSCFAs in R patients (n = 9) were significantly higher than that in NR patients (n = 31) (p < 0.001). Progression-free survival (PFS) was significantly longer in patients with high fSCFAs than patients with lower fSCFAs (median 5.5 vs. 1.4 months, hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.17-0.72). In melanoma patients, PFS was also significantly longer in patients with high fSCFAs than that with lower fSCFAs (median 6.1 vs. 1.4 months, HR 0.30, 95% CI 0.10-0.89).

Conclusions

The fSCFA could predict the efficacy of PD1i.

Clinical trial identification

UMIN000023303.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Novartis Pharma.

Disclosure

M. Nomura: Research grant / Funding (self): Novartis Pharma. All other authors have declared no conflicts of interest.

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