SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer

TAKE-AWAY POINTS This multicenter international study randomized patients with metastatic colorectal cancer (mCRC) between first-line systemic chemotherapy alone and first-line systemic chemotherapy combined with yttrium-90 (Y-90) resin microspheres. Eligible patients with nonresectable liver-only or liver-dominant mCRC and no prior systemic chemotherapy were randomized 1:1 between both arms. The control arm consisted of mFOLFOX6 (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) plus/minus bevacizumab (investigator’s discretion), and the treatment arm consisted of the same regimen with a single, whole-liver dose of SIR-Sphere Y-90 resin microspheres (Sirtex Medical Inc.) administered on day 3 or 4 of either cycle 1 or 2. Five hundred thirty patients were randomized, and the results showed no statistically significant difference in progression-free survival at any site between the two arms (median, 10.2 vs 10.7 months; P = .43). However, with the addition of Y-90 microspheres, there was a statistically significant 7.9-month improvement in median progressionfree survival in the liver (12.6 vs 20.5 months; P = .002). Objective response rates (complete + partial response) were not statistically significantly different at any site but were statistically significantly improved in the liver (68.8% vs 78.7%; P = .042). Grade 3 or higher adverse events slightly increased in the mFOLFOX plus Y-90 arm, including a 3.7% incidence of gastric or duodenal ulcers.