SIRFLOX Study Published for Sirtex's SIR-Spheres Y-90 Resin Microspheres to Treat Metastatic Colorectal Cancer

February 25, 2016—Sirtex Medical Limited announced that the results of the SIRFLOX study of SIR-Spheres Y-90 resin microspheres have been published online by Prof. Guy A. van Hazel, MD, et al in the Journal of Clinical Oncology, a publication of the American Society of Clinical Oncology (ASCO). In May 2015, the company announced that the initial SIRFLOX study findings were reported in an oral abstract presentation at the ASCO Annual Congress in Chicago, Illinois.

SIRFLOX is a randomized phase 3 trial comparing first-line mFolfox6 (with or without bevacizumab) versus mFolfox6 (with or without bevacizumab) plus selective internal radiation therapy (SIRT, using SIR-Spheres Y-90 resin microspheres) in patients with metastatic colorectal cancer (mCRC).

The SIRFLOX study recruited 530 patients who had been diagnosed with unresectable mCRC at 87 medical centers in Australia, Europe, Israel, New Zealand, and the United States between October 2006 and April 2013. Of these 530 patients, 263 control patients were randomized to be treated with the mFolfox6 regimen of 5FU, leucovorin and oxaliplatin, with the biological agent bevacizumab allowed at the local investigator's discretion. The other 267 patients received SIRT with SIR-Spheres Y-90 resin microspheres in addition to the mFolfox6 chemotherapy regimen (± bevacizumab).

The primary endpoint of SIRFLOX was progression-free survival (PFS) at any site. Patients in the SIRFLOX control arm had a PFS at any site of 10.2 months versus 10.7 months in the SIRT arm, but this difference was not statistically significant (hazard ratio (HR), 0.93; P = .43). However, in respect to the study's key secondary endpoint of median PFS in the liver, which is the organ that SIR-Spheres Y-90 resin microspheres directly target, was 12.6 months versus 20.5 months in the control versus SIRT groups by competing risk analysis (HR, 0.69; P = .002), representing a 31% gain with the addition of SIRT. In addition, although the objective treatment response rate at any site was similar (control, 68.1% vs SIRT, 76.4%; P = .113), this improved in the liver with the addition of SIRT (control, 68.8% vs SIRT, 78.7%; P = .042), with complete responses in the liver increasing over threefold (control, 1.9% vs SIRT, 6%; P = .02).

Grade 3 adverse events were reported in 73.4% and 85.4% of patients in the control versus SIRT groups (P = .516), including recognized SIRT-related effects. The investigators found that the safety profile of the combined therapy was expected and consistent with previous studies, advised the company.

As reported by Sirtex Medical, the investigators concluded, “The median 20.5-month liver PFS for patients treated with chemotherapy plus SIRT represents a substantial prolongation of local disease control compared to systemic chemotherapy alone, which was a median 12.6 months.”

For the secondary outcome of overall survival, the investigators stated, “During the 7-year recruitment period of the study, when it became evident that improved patient care and new chemotherapy regimens were extending survival for mCRC patients receiving first-line chemotherapy treatment, a decision was made to preplan a combined survival analysis including data from SIRFLOX and two additional randomized studies, FOXFIRE and FOXFIRE Global.”

They continued, “In all three studies, SIRT has been added to oxaliplatin-based chemotherapy in an almost identical patient population. The FOXFIRE and FOXFIRE Global studies have completed accrual and combined with SIRFLOX have a total recruitment of over 1,100 patients; this provides adequate power to detect a survival advantage.” Findings are expected to be reported in 2017.

SIR-Spheres Y-90 resin microspheres are approved for the treatment of inoperable liver tumors in Australia, the European Union, Argentina, Brazil, and several countries in Asia such as India, Singapore, and Turkey. The product is also supplied for this use in countries such as Hong Kong, Israel, Malaysia, New Zealand, Taiwan, and Thailand.

In the United States, SIR-Spheres Y-90 resin microspheres are approved by the US Food and Drug Administration for the treatment of nonresectable metastatic liver tumors from primary colorectal cancer in combination with intrahepatic artery chemotherapy using floxuridine, noted Sirtex Medical.