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.
Resources from the same session
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract