SIRFLOX Study in Metastatic Colorectal Cancer

The phase III SIRFLOX study assessed whether the addition of selective internal radiation therapy (SIRT) to standard chemotherapy was more effective than chemotherapy alone in patients with metastatic colorectal cancer (CRC). Eligible patients had extrahepatic disease that had not yet been treated with chemotherapy. SIRT incorporates Yttrium-90-resin microspheres that are delivered to the liver lesion via catheter to treat metastases, explains Howard S. Hochster, MD.

For the primary endpoint of PFS at any site, the median in the SIRT arm was 10.7 months versus 10.2 months (HR = 0.93; P = .43). However, the median PFS in the liver was 20.5 months with SIRT compared with 12.6 months without (HR = 0.69; P = .002). The ORR in the liver was 68.6% without SIRT and 78.7% with SIRT (P = .042).

Prospective, non-controlled studies evaluating the use of these beads in advanced disease settings demonstrated an ability to shrink tumors and control liver disease. It is not surprising that more liver control was accomplished with the interventional therapy in a randomized trial, notes Hochster, but the important concern is whether SIRT can change the natural history of the disease and help people live longer. The results of one study to date have not demonstrated an improvement in overall survival (OS) but did reveal a biological impact, notes Richard L. Goldberg, MD.

SIRT is a valuable tool, but it is not yet understood how to optimally use it, comments Goldberg. Clinicians today are discovering how to better incorporate breaks in therapy and optimize use of surgery, ablation, and hepatic arterial infusion, says Goldberg, which can all impact the natural history of advanced colorectal cancer.

SIRFLOX is the first of three randomized controlled trials in a preplanned combined analysis of SIRT’s impact on OS. SIRFLOX, FOXFIRE, and FOXFIRE Global have accrued a total of 1103 patients. Combined analysis of OS data from these three trials will be examined in 2017.