Combinations of VEGFR-TKIs plus immune checkpoint inhibitors (ICIs) anti-PD-1 are the standard first-line therapy for patients (pts) with metastatic renal cell carcinoma (mRCC). Intestinal microbiota composition could influence ICIs activity in mRCC and other cancers, while FMT is currently used to regulate microbiota-related diseases. TACITO trial (NCT04758507) investigated whether FMT could increase the efficacy of VEGFR-TKI+ICI combinations in mRCC.
Methods
mRCC pts treated with axitinib+pembrolizumab (axi+pembro) in first-line were randomized (1:1) to FMT or placebo (pbo). Pts received direct infusion in the colon of stools from a donor or pbo at baseline (within 8 weeks from the start of axi+pembro, FMT1), followed by oral capsules with the same frozen stools or pbo at 90 (FMT2), and 180 days (FMT3), respectively. The donor was a mRCC patient (pt) who achieved complete and long-lasting response to ICIs. The primary endpoint was to increase of ≥20% the rate of pts with no disease progression at one year (1-year PFS rate) with FMT vs. pbo. Secondary endpoints were median PFS, overall survival (OS), objective response rate (ORR), and microbiota characterization.
Results
50 pts were randomized to FMT (IMDC risk: 28% favorable, 72% intermediate-poor) or pbo (32% favorable, 68% intermediate-poor). 44 pts were evaluable for the primary endpoint (24 in the FMT group and 20 in the pbo). The 1-year PFS rate was 66.7% with FMT vs. 35.0% with pbo, p=0.036. In the overall population, after a median follow-up of 28.0 mos, the mPFS was 14.2 (95%CI, 0.9–27.6) vs. 9.2 (95%CI, 3.0–15.4) mos and the mOS was not reached vs. 25.3 (95%CI, 17.1–33.6) mos with FMT and pbo, respectively. The ORR was 54% vs. 28% in the FMT arm compared to pbo; 38% vs. 44% had SD and 8% vs. 28% had PD. Safety: only 1 pt in the pbo arm reported FMT/pbo-related adverse event (grade 3 oral mucositis) and discontinued capsules assumption.
Conclusions
The preliminary results of TACITO trial show for the first time the role of FMT in increasing the activity of ICIs-based therapies in mRCC pts.
Clinical trial identification
NCT04758507.