Phase II data derived from the first randomised trial comparing immunotherapy outcomes post-FMT from immunotherapy responders versus placebo.
Faecal microbiota transplantation (FMT) could enhance the effectiveness of immunotherapy in advanced metastatic renal cell carcinoma (mRCC), according to new research.
In the phase IIa TACITO trial, the first randomised trial to compare immunotherapy outcomes following FMT from immunotherapy responders versus placebo, median progression-free survival was markedly longer in the donor-derived FMT group. A total of 45 patients with advanced kidney cancer enrolled in the trial.
Professor Roberto Iacovelli, co-principal investigator added: “[data showed] 24 months versus nine months in the control group—corresponding to a 50 percent reduction in the risk of disease progression.”
This is notable considering that evidence shows immunotherapy does not appear to benefit the majority of patients.
Professor Giampaolo Tortora, Full Professor of Medical Oncology at Università Cattolica del Sacro Cuore explained: “The gut microbiota is known to influence the immune system, and in kidney cancer several factors—such as marked angiogenesis and inflammatory mediators like IL-6—can reduce the effectiveness of immunotherapy”.
Dr Gianluca Ianiro, the study’s principal investigator added that the findings “provide further evidence that the gut microbiota is a key modulator of immunotherapy response… FMT from carefully selected donors may become an important complementary strategy to improve outcomes in metastatic renal cell carcinoma, likely by providing an immunological stimulus that enhances treatment response.”
Leveraging FMT for enhanced immunotherapy outcomes in advanced cancer
FMT from carefully selected donors may become an important complementary strategy to improve outcomes in metastatic renal cell carcinoma, likely by providing an immunological stimulus that enhances treatment response"
Patients were initially treated with the standard first-line combination of immune checkpoint inhibitor pembrolizumab and anti-angiogenic therapy axitinib, then randomised to receive either donor-derived FMT or placebo.
This verified whether FMT from donors who had achieved a complete response to immunotherapy could improve clinical outcomes in patients with mRCC.
While one-year data showed that 70 percent of patients in the donor-derived FMT group were free from disease progression, compared with 41 percent with placebo, this was not statistically significant. However, several secondary endpoint findings showed strong promise.
Another key finding showed a higher objective response rate (52 percent) in the donor-derived FMT group compared with 32 percent for placebo.
Dr Chiara Ciccarese, co–first author of the study and oncology researcher at Università Cattolica del Sacro Cuore also noted that for patients with intermediate or poor prognostic risk, “this finding is particularly relevant, as these patients typically have fewer therapeutic options and worse outcomes”.
The study ‘Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial’ was published in Nature Medicine.
Recent phase II data further affirms benefit of Merck’s anti-PD-1 therapy, particularly as a combination treatment. Using pembrolizumab with Moderna’s mRNA-based intismeran autogene (mRNA-4157 or V940) reduced the risk of disease recurrence or death in high-risk melanoma patients by 49 percent compared to Keytruda alone.
