Evolving Approaches for Controlling Liver Metastases in CRC - Episode 6

SIRFLOX Study in Liver-Metastatic Colorectal Cancer

The SIRFLOX trial represents the first level 1 evidence demonstrating the efficacy of Yttrium-90 resin microspheres, or selective internal radiation therapy (SIRT), for patients with metastatic colorectal cancer (CRC), states David Liu, MD. Importantly, he adds, any treatment that can prevent or delay progression within the liver has an opportunity to improve overall survival, since liver involvement is the leading source of mortality in the majority of patients with metastatic CRC.

While there is an advantage associated with applying SIRT as first-line therapy, the primary endpoint of the SIRFLOX trial, progression-free survival (PFS), was not reached, notes Volker Heinemann, MD. However, the secondary endpoint of PFS in the liver was improved in the study. In those treated with SIRT plus chemotherapy, the liver-specific PFS was 20.5 months compared with 12.6 months with chemotherapy alone (HR = 0.69; P = .002). These findings represent a major advantage with the addition of SIRT to first-line treatment, says Heinemann.

The SIRFLOX study showed that SIRT is important for controlling disease in the liver, adds Marwan Fakih, MD. An additional 10% of patients responded to therapy when Yttrium-90 resin microspheres were added to chemotherapy, demonstrating that the procedure can also help downstage disease in the liver, Fakih adds. In the study, the objective response rate (ORR) in the liver was 78.7% with SIRT versus 68.6% without (P = .042).

Therapy with Yttrium-90 resin microspheres is relatively well tolerated, comments Liu. The incidence of non-SIRT related toxicities, primarily neutropenia and some types of febrile neutropenia, correlates with dose intensification of chemotherapeutic regimens. Complications related to SIRT include radiation-induced liver disease, where the liver deactivates and enters into an inflammatory cycle as a result of radiation exposure, explains Liu. Overall, adverse events associated with SIRT were infrequent and predictable.