SIRFLOX Regimen Delays Liver Progression in Metastatic Colorectal Cancer

February 25, 2016
Leah Lawrence

The addition of selective internal radiation therapy with yttrium-90 resin microspheres to standard FOLFOX chemotherapy did not improve progression-free survival in patients with metastatic colorectal cancer, but it did significantly delay disease progression in the liver.

The addition of selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres to standard FOLFOX chemotherapy did not improve progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), but it did significantly delay disease progression in the liver, according to the results of a study published in the Journal of Clinical Oncology.

“SIRFLOX is the first large phase III randomized controlled trial to assess the efficacy and safety of a liver-directed therapy in patients with mCRC,” wrote researcher Guy A. van Hazel, MBBS, of the University of Western Australia, and colleagues. “Unlike previous studies combining SIRT with first-line fluoropyrimidine-based chemotherapy in patients with mCRC, the SIRFLOX study failed to show an improvement in median PFS at any site with the addition of SIRT.”

The trial included 530 patients with chemotherapy-naive disease and liver metastases. The patients were randomly assigned to either modified FOLFOX (n = 263) or modified FOLFOX plus SIRT (n = 267) plus or minus bevacizumab. The primary endpoint was PFS.

The median PFS was 10.2 months for FOLFOX vs 10.7 months for SIRT plus FOLFOX (hazard ratio [HR], 0.93 [95% CI, 0.77–1.12]; P = .43). In addition, objective response rates were similar between the two arms.

The median PFS in the liver was 12.6 months for FOLFOX alone compared with 20.5 months for FOLFOX plus SIRT, a 31% risk reduction (HR, 0.69 [95% CI, 0.55–0.90]; P = .002). The objective response rate in the liver was also improved with the addition of SIRT, from 68.8% with FOLFOX alone to 78.7% with SIRT (P = .042).

“The median 20.5-month liver PFS for patients treated with chemotherapy plus SIRT represents a substantial prolongation of local disease control compared with systemic chemotherapy alone (median, 12.6 months). Because, to the best of our knowledge, this is the first study to evaluate PFS in the liver, there are no other studies that provide context for this result,” the researchers wrote. “Overall survival data from a combined analysis of SIRFLOX and two other first-line studies are awaited to determine whether this substantial gain in control of existing liver metastases translates into a significant gain in survival.”

Treatment-emergent grade 3 or higher adverse events occurred in 73.3% of patients assigned FOLFOX compared with 85.4% of patients assigned SIRT. Patients on SIRT experienced significantly more hematologic toxicities compared with the control arm (P < .05).

“The potential long-term impact on survival from integrating SIRT into the first-line treatment of mCRC will be evident when the results of the preplanned combined analysis of SIRFLOX, FOXFIRE, and FOXFIRE Global are available,” the researchers wrote.