When immunotherapy stops working for advanced stomach or colon cancer, patients often have few options left. This small, early-stage study tested a new idea: what if we could 'reset' a patient's gut bacteria to help their immune system fight back? Ten patients whose cancers had become resistant to standard immunotherapy received a transplant of healthy donor gut bacteria, taken in capsule form, alongside continued immunotherapy treatment. The most important finding was that this combination was safe, with no serious side effects reported. In terms of early results, two out of the ten patients (20%) saw their tumors shrink, and four patients (40%) had their disease stop growing for a period. The researchers saw that patients who benefited seemed to have new, helpful bacteria from the donor take hold in their gut, and their blood showed signs of a more active immune system. They also identified specific patterns of gut bacteria linked to a better response to treatment. This is just a first step, but it shows that combining a gut bacteria transplant with immunotherapy is a safe and feasible path to explore for patients who have otherwise run out of effective treatments.
Could a gut bacteria transplant help when immunotherapy stops working for stomach cancer?
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What this means for you:
Combining a gut bacteria transplant with immunotherapy was safe and showed early promise for some patients with resistant stomach cancer. What this means for you:
Combining a gut bacteria transplant with immunotherapy was safe and showed early promise for some patients with resistant stomach cancer. View Original Abstract ↓
BACKGROUND: The discovery and therapeutic application of immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. The gut microbiome's impact on immune modulation is a promising area for overcoming resistance to immunotherapy.
METHODS: This study (NCT04130763) is an open-label, single-arm, single-center, phase I study assessing the safety and efficacy of fecal microbiota transplantation (FMT) from healthy donors in 10 patients with advanced GI cancer resistant to anti-programmed death-ligand 1 (PD-(L)1) treatment. 10 patients with histologically confirmed, unresectable, or metastatic GI cancers (8 gastric, 2 colorectal) who were refractory to anti-PD-(L)1 treatment were enrolled. Patients received initial FMT treatment via oral capsules (60 capsules), followed by a combination therapy phase, where maintenance FMT (10 capsules per treatment) was paired with nivolumab at 3 mg/kg every 2 weeks for six cycles. Serial biomarker assessments were conducted through both fecal and blood sampling.
RESULTS: The combination of FMT and anti-PD-1 treatment was well tolerated with no serious adverse events. The objective response rate was 20% and the disease control rate was 40%. Clinical benefits were associated with colonization of donor-derived immunogenic microbes, and an activated immune status reflected by peripheral immune cell populations. Moreover, microbial signatures were identified for anti-programmed cell death protein-1 (PD-1) responsiveness and validated in an independent cohort.
CONCLUSIONS: This phase I study demonstrates the feasibility and safety of combining FMT with anti-PD-1 therapy in patients with ICI-refractory gastric cancer. The observed preliminary efficacy signals and identified microbial signatures generate hypotheses for future trials to investigate microbiome-based approaches to enhance immunotherapy efficacy.
TRIAL REGISTRATION NUMBER: NCT04130763.