by A recent study published in eClinicalMedicine has shown promising results in the use of fecal microbiota transplantation (FMT) to enhance the efficacy of anti-programmed cell death protein 1 (PD-1) therapy for patients with microsatellite stable metastatic colorectal cancer (CRC). This research offers new hope for those with this type of cancer, which is one of the most prevalent forms of cancer worldwide and a leading cause of cancer-related deaths.
Metastatic CRC is typically treated with therapies that target epidermal growth factor (EGF) or vascular endothelial growth factor (VEGF) receptors, combined with chemotherapy. However, third-line treatment options are limited and often associated with low efficacy and adverse events. Immune checkpoint inhibitors have shown great promise in improving treatment effectiveness for various cancers, including CRC with high microsatellite instability or mismatch repair deficiency. However, these inhibitors are less effective for microsatellite stable or mismatch-repair proficient CRC.
Based on previous observations that the gut microbiota can improve immune responses, researchers explored the potential of FMT to enhance treatment efficacy by reprogramming the tumor microenvironment in CRC. The study was conducted as a single-arm, open-label, Phase II clinical trial, combining FMT with fruquintinib (a tyrosine kinase inhibitor of VEGF receptors) and tislelizumab (a monoclonal antibody PD-1 inhibitor) as a third-line treatment for microsatellite stable metastatic CRC.
The study included patients above the age of 18 with progressive or metastatic CRC who had experienced intolerance or disease progression despite second-line chemotherapy. They also needed to have adequate organ function and at least one measurable tumor. Polymerase chain reaction (PCR) assay, immunohistochemistry, and next-generation sequencing confirmed microsatellite stability. Patients with concomitant cancer, autoimmune disease, a history of immunotherapy or organ transplantation, or who were prescribed immunosuppressive therapy were excluded from the study.
FMT was conducted after a phase of native microbiota depletion using orally administered stool capsules customized to each patient. Fruquintinib was given orally, and tislelizumab was administered intravenously. The primary endpoint of the study was progression-free survival, while secondary outcomes included overall response rate, duration of response, disease control rate, clinical benefit rate, and overall survival. Tumor responses were assessed by independent radiologists.
The combination treatment of FMT with tislelizumab and fruquintinib was found to be safe and resulted in improved survival for patients with microsatellite stable metastatic CRC. The study showed a 9.6-month increase in mean progression-free survival and a 13.7-month increase in mean overall survival. Additionally, the overall response rate was 20% higher, and the disease control rate was 95% higher compared to existing treatments.
Gut microbiome analysis revealed that post-treatment microbiome compositions had a higher abundance of bacteria from the Lachnospiraceae family, known to be favorable for immunotherapy. However, the abundance of bacteria from the Bifidobacterium family, which increases immune tolerance, was lower after treatment.
Overall, the combination treatment of FMT with fruquintinib and tislelizumab showed manageable adverse reactions and demonstrated significant antitumor activity. This approach holds promise for improving outcomes in patients with microsatellite stable metastatic CRC. Further research is needed to validate these findings and explore the potential of FMT as a treatment strategy for CRC and other types of cancer.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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