Fecal microbiota transplantation boosts survival in metastatic colorectal cancer treatment

In a recent study published in eClinicalMedicine, researchers assess the use of fecal microbiota transplantation to enhance the efficacy of anti-programmed cell death protein 1 (PD-1) therapy for patients with microsatellite stable metastatic colorectal cancer.

Study: Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN215). Image Credit: Peakstock / Shutterstock.com

Background

Colorectal cancer is one of the three most prevalent forms of cancer throughout the world and, as a result, a major cause of cancer-related mortality. The current standard first- and second-line treatments for metastatic colorectal cancer include therapies targeting epidermal growth factor (EGF) or vascular endothelial growth factor (VEGF) receptors combined with fluorouracil-based chemotherapy. However, there remains a lack of third-line treatments, with existing options often associated with low efficacy and a high rate of adverse events.

Immune checkpoint inhibitors have significantly improved the treatment effectiveness for various cancers and have been specifically recommended for the treatment of tumors with high microsatellite instability or mismatch repair deficiency, including colorectal cancers. However, most metastatic colorectal cancers are of the microsatellite stable or mismatch-repair proficient phenotype, for which immune checkpoint inhibitors are less effective.

Based on previous observations that the gut microbiota can improve immune responses, fecal microbiota transplantation has been explored to enhance treatment efficacy by reprogramming the tumor microenvironment in colorectal cancer.

About the study

The present study was a single-arm, open-label, phase II clinical trial to evaluate the safety and efficacy of combining fecal microbiota transplantation with fruquintinib, which is a small-molecule tyrosine kinase inhibitor of VEGF receptors, and tislelizumab, a monoclonal antibody PD-1 inhibitor. This combination was explored as a third-line treatment option for microsatellite stable metastatic colorectal cancers.

Patients above the age of 18 with progressive or metastatic colorectal cancer and an intolerance to or progression despite second-line chemotherapy were included in the study. The included patients were required to have adequate renal, hepatic, and hematological function and at least one measurable tumor. Polymerase chain reaction (PCR) assay, immunohistochemistry, and next-generation sequencing were used to confirm microsatellite stability.

Individuals with another concomitant cancer, autoimmune disease, a history of immunotherapy or organ transplantation, any factors that would impact the absorption of oral drugs, and those prescribed systemic immunosuppressive therapy were excluded from the study. After a phase of native microbiota depletion, fecal microbiota transplantation was conducted using orally administered stool capsules that were customized to the patient, along with orally administered fruquintinib and intravenously administered tislelizumab.

Progression-free survival was the primary endpoint, whereas overall response rate, duration of response, disease control rate, clinical benefit rate, and overall survival were secondary outcomes. Independent radiologists assessed tumor responses. The treatment was continued until the participant withdrew consent, unacceptable levels of toxicity were observed, the study was completed, the investigator decided to terminate the study, or the participant died.

Fecal and peripheral blood samples were serially collected to analyze the gut microbiome and exploratory biomarker levels. Pyrosequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) amplicon from genomic DNA extracted from the stool samples was used to analyze the gut microbiome. T-cell receptor sequencing from peripheral blood mononuclear cells (PBMCs) was conducted to explore potential biomarkers.

Study findings

The combination treatment of fecal microbiota transplantation with tislelizumab and fruquintinib was found to be manageably safe and resulted in improved survival in patients with microsatellite stable metastatic colorectal cancer. More specifically, the intervention resulted in a 9.6-month increase in mean progression-free survival and a 13.7-month increase in mean overall survival, as well as 20% and 95% higher overall response and disease control rates, respectively.

The gut microbiome analyses also showed that post-treatment microbiome compositions had a relatively greater abundance of bacteria belonging to the family Lachnospiraceae, which are known to be favorable for immunotherapy. The abundance of bacteria belonging to the Bifidobacterium family, which increases immune tolerance, was also found to be lower after treatment.

The toxicity profile of this combination treatment was manageable, and significant antitumor activity was observed.

Conclusions

Fecal microbiota transplantation combined with fruquintinib and tislelizumab had manageable adverse reactions. Importantly, this treatment approach significantly increased overall and progression-free survival rates in patients with microsatellite stable metastatic colorectal cancer.

Journal reference:
  • Zhao, W., Lei, J., Ke, S., et al. (2023). Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN215). eClinicalMedicine 66. doi:10.1016/j.eclinm.2023.102315
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Sidharthan, Chinta. (2023, November 15). Fecal microbiota transplantation boosts survival in metastatic colorectal cancer treatment. News-Medical. Retrieved on October 31, 2024 from https://www.news-medical.net/news/20231115/Fecal-microbiota-transplantation-boosts-survival-in-metastatic-colorectal-cancer-treatment.aspx.

  • MLA

    Sidharthan, Chinta. "Fecal microbiota transplantation boosts survival in metastatic colorectal cancer treatment". News-Medical. 31 October 2024. <https://www.news-medical.net/news/20231115/Fecal-microbiota-transplantation-boosts-survival-in-metastatic-colorectal-cancer-treatment.aspx>.

  • Chicago

    Sidharthan, Chinta. "Fecal microbiota transplantation boosts survival in metastatic colorectal cancer treatment". News-Medical. https://www.news-medical.net/news/20231115/Fecal-microbiota-transplantation-boosts-survival-in-metastatic-colorectal-cancer-treatment.aspx. (accessed October 31, 2024).

  • Harvard

    Sidharthan, Chinta. 2023. Fecal microbiota transplantation boosts survival in metastatic colorectal cancer treatment. News-Medical, viewed 31 October 2024, https://www.news-medical.net/news/20231115/Fecal-microbiota-transplantation-boosts-survival-in-metastatic-colorectal-cancer-treatment.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Researchers uncover why the TP53 gene is especially prone to mutations in cancer