Sirflox: Randomised phase III trial comparing first-line mFOLFOX6 +/- bevacizumab (BEV) versus mFOLFOX6 +/- BEV + selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC)-analysis by presence or absence of extra-hepatic metastases, BEV treatment and site of first progression.

Abstract

Background: The SIRFLOX study assessed the efficacy and safety of combining FOLFOX chemotherapy (+/- bev) with SIRT as first-line treatment of patients with CRC liver metastases. Planned sub-analyses analyses included +/- extra-hepatic metastases, +/- bev and site of first progression. Method(s): SIRFLOX was an international, multi-centre, open-label, RCT in chemotherapy-naive patients with non-resectable, liver-only or liverdominant mCRC. Arm A: mFOLFOX6 +/- bev vs. arm B: mFOLFOX6 +/- bev +SIRT using yttrium-90 resin microspheres (SIR-Spheres; Sirtex) administered once with cycle 1. The primary endpoint was overall PFS using RECIST v1.0. Stratification variables included +/- extra-hepatic metastases, and +/- bev. Liver PFS was assessed by Competing Risk analysis. First progression was judged by independent reader blinded to study arm. Result(s): 530 patients were randomised (A, n = 263; B, n = 267), 212 (40%) had EHD; 292 (55%) received bev. Median follow-up was 36.1 months. Median overall PFS was 10.2 vs. 10.7 months in A vs. B, respectively (p = 0.428). Median liver PFS was 12.6 vs. 20.5 months in A vs. B (p = 0.002). Median Liver PFS was 12.4 vs. 21.1 months in A vs. B (p = 0.003) for patients with liver-only metastases, and 12.6 vs. 16.7 months (p = 0.147) for those with liver and extra-hepatic metastases. Median Liver PFS was 10.6 vs. 18.9 months in A vs. B (p = 0.028) for patients with ITT -bev, and 12.7 vs. 21.0 months (p = 0.018) for those with ITT +bev. The site of first progression was more frequently the liver (+/- other sites) in A [164/ 178, 92.1%] vs. B [120/166, 72.3%] (p < 0.001). All-causality grade >=3 adverse events occurred in 73.3% vs. 85.4% (NS) of patients in A vs. B. Conclusion(s): In first-line treatment of patients with non-resectable CRC liver metastases, adding SIRT to FOLFOX-based chemotherapy failed to improve overall PFS. The addition of SIRT significantly extended median liver PFS and reduced the frequency that first disease progression occurred in the liver.