The TACITO-II trial has revealed that fecal microbiota transplantation (FMT) can significantly boost the effectiveness of immunotherapy in patients with metastatic renal cell carcinoma (RCC). The study, a phase two prospective randomized trial, investigated the impact of FMT in combination with pembrolizumab and axitinib, a standard first-line treatment for metastatic RCC.
Trial Design and Methodology
The trial randomized 50 patients with metastatic RCC in a 1:1 ratio to either FMT plus pembrolizumab and axitinib or placebo plus pembrolizumab and axitinib. The FMT procedure involved an initial colonoscopy for direct infusion of stool from a donor with exceptional response to immunotherapy, followed by frozen oral capsules at three and six months after the initial transplant. The primary endpoint was the one-year progression-free survival (PFS) rate, with the study designed to detect a 20% absolute increase in this rate.
Key Findings
Preliminary data from 44 patients with a minimum follow-up of 12 months showed that FMT significantly improved the one-year PFS rate. The FMT arm achieved a 66.7% one-year PFS rate compared to 35% in the placebo arm, representing an absolute increase of over 30%. The median PFS in the FMT group was 14.2 months, compared to 9.2 months in the placebo group. Overall survival data are still immature, but early results indicate a separation of the survival curves, with the median overall survival not reached in the FMT group compared to 25.3 months in the placebo group.
Furthermore, FMT nearly doubled the overall response rate to pembrolizumab plus axitinib. While no complete responses were observed, only 8% of patients in the FMT arm were primary refractory. Importantly, FMT was well-tolerated, with no adverse events directly related to the transplantation procedures and no increase in the rate of severe adverse events associated with pembrolizumab and axitinib.
Implications and Future Directions
Dr. Chiara Ciccarese, a medical oncologist from Rome, Italy, emphasized the novelty of the trial, stating that it demonstrates the possibility of transferring immune response through microbiota transplantation. She highlighted the safety and feasibility of the procedure, with 90% dose intensity achieved, and advocated for further investigation.
Future research will focus on analyzing the microbiota composition of both the patient donor and the patients themselves to understand how FMT modifies the gut microbiome and influences treatment response. This includes characterizing the ideal microbiome composition of the donor to design prospective phase III trials. According to Dr. Ciccarese, identifying patients with a "bad" microbiome who are less likely to respond to immunotherapy could allow for selection of those most suitable for FMT.
For current clinical practice, Dr. Ciccarese advises using antibiotics only when necessary and paying attention to patient diet, recognizing that microbiome composition and conditions leading to dysbiosis may be key to enhancing immunotherapy response in the future.
