Radioembolization as a Treatment Strategy for Metastatic Colorectal Cancer to the Liver: What Can We Learn from the SIRFLOX Trial?

In the setting of liver metastases from colorectal cancer (CRC), radioembolization with yttrium-90 has been used to treat chemotherapy refractory disease with a growing interest to establish its efficacy in prospective trials combined with first- and second-line chemotherapy. SIRFLOX is an ongoing, multi-center, phase 3 randomized trial comparing first-line chemotherapy alone or in combination with yttrium-90 radioembolization in patients with CRC who have isolated liver metastases or liver-dominant metastases. Preliminary results from SIRFLOX demonstrate that radioembolization combined with first-line chemotherapy is safe and feasible. There was no significant difference in median overall progression-free survival (PFS) between the combined radioembolization-chemotherapy and chemotherapy-only arms (10.7 versus 10.2 months). Although the trial did not meet its primary endpoint of improved median PFS, there was a significant increase in the median hepatic PFS (20.5 versus 12.6 months; p = 0.02) favoring the combination arm. Thus, combining radioembolization with chemotherapy in the first-line setting may be most effective for liver-limited metastatic CRC. Since radioembolization targets liver disease, it is plausible that the trial failed to achieve an improvement in PFS given that 40 % of the SIRFLOX population had extra-hepatic disease. It is also possible that the overall median PFS may be a poor surrogate endpoint, and other endpoints like overall survival still needs to be delineated in this setting. In addition, it is crucial to document improvement or delay in time to deterioration in quality of life symptom endpoints in this population. SIRFLOX is the first of three prospective studies that assess the efficacy of adding radioembolization to first-line chemotherapy, and the combined data from these trials will provide the necessary power for an overall survival analysis. The final results of SIRFLOX will be eagerly awaited to determine if the increased hepatic PFS in preliminary data will translate to increased overall survival benefit.