SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bev in patients (pts) with metastatic colorectal cancer (mCRC).

3502 Background: The SIRFLOX study was designed to assess the efficacy and safety of combining FOLFOX chemotherapy (± bev) with SIRT using yttrium-90 (Y-90) resin microspheres as first-line treatment of pts with liver metastases from mCRC. Methods: SIRFLOX was an international, multi-center, open-label, RCT in chemotherapy-naïve pts with non-resectable, liver only or liver dominant (liver plus lung and/or lymph node metastases) mCRC. Arm A: mFOLFOX6 ± bev was compared to arm B: mFOLFOX6 + SIRT (SIR-Spheres; Sirtex) administered once with cycle 1 ± bev until disease progression. The primary endpoint was progression free survival (PFS) using RECIST v1.0. Stratification variables included presence of extra hepatic disease (EHD; liver only v liver dominant), degree of liver involvement ( ≤ 25% v > 25%), and treatment with bev (at clinician discretion). Results: From Oct 2006 to Apr 2013,530 pts were randomised (arm A, n = 263; arm B, n = 267), 212 (40%) had EHD. Median follow-up was 36.1 months. The median overall PFS was 10.2 v 10.7 months in arms A v B respectively (hazard ratio [HR]: 0.93; 95% CI 0.77–1.12; p=0.428) by Kaplan Meier analysis. The median PFS in the liver was 12.6 v 20.5 months in arm A v B (HR: 0.69; 95% CI 0.55–0.90; p = 0.002) by competing risk analysis. Overall response rate (PR + CR) was 68.0% v 76.4% in arm A v B, respectively (p = 0.113). Hepatic response rate was 68.8% v 78.7% in arm A v B (p = 0.042), including CR rate 1.9% v 6.0% (p = 0.02). The liver resection rate was 13.7% v 14.2% in arm A v B (p = 0.857). Adverse events ≥ grade 3 were noted in 73.3% v 85.4% of pts in arm A v B. Most common toxicities were hematologic; 32.9% v 51.2% and gastrointestinal; 21.2% v 32.9%, including gastric ulcer 0.0% v2.4%. Conclusion: In first-line treatment of pts with non-resectable CRC liver metastases, the addition of SIRT to standard chemotherapy failed to improve overall PFS. However, median liver PFS was significantly extended. The addition of SIRT was associated with acceptable toxicity. Overall survival analyses, combining data from SIRFLOX and two other ongoing studies in this disease setting, are awaited. Clinical trial information: NCT00724503.