SIRT Fails to Boost PFS With mFOLFOX6 For CRC Liver-Dominant Metastases

Progression-free survival is unaffected by use of selective internal radiotherapy in patients undergoing first-line chemotherapy for colorectal cancer liver-dominant metastases

medwireNews: The addition of selective internal radiation therapy (SIRT) to chemotherapy, and bevacizumab where appropriate, does not extend progression-free survival (PFS) for colorectal cancer (CRC) patients with treatment-naive, liver-dominant metastases, SIRFLOX trial findings indicate.

The data did suggest, however, that the addition of SIRT to the modified FOLFOX6 regimen, with or without bevacizumab, prolonged the secondary endpoint of PFS in the liver, the authors report in the Journal of Clinical Oncology.

“[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”, comment Guy van Hazel, from the University of Western Australia in Perth, and co-investigators.

The phase III trial primary endpoint of PFS at any site was a median of 10.7 months in the 267 patients given modified FOLFOX6 plus SIRT using yttrium-90 resin microspheres, and bevacizumab at the investigator’s discretion, versus 10.2 months for the 263 patients given chemotherapy with or without bevacizumab.

The objective response rate at any site was also comparable for the SIRT and no-SIRT groups, at 68.1% and 76.4%, respectively, although there was a significantly higher objective response rate in the liver with SIRT, at 68.8% versus 78.7% in the control patients.

And median PFS in the liver was significantly longer in patients given SIRT than controls, at 20.5 months versus 12.6 months and a hazard ratio of 0.69, and this benefit remained after adjusting for tumour burden, performance status and receipt of bevacizumab.

Analysis showed that the SIRT-treated patients were significantly less likely to experience their first progression in the liver than controls (52.4 vs 77.0%).

Patients given SIRT were significantly more likely to experience their first progression outside of the liver than patients given chemotherapy alone; although this largely occurred in the lungs, SIRT-treated patients did not experience lung metastases at a significantly earlier time than controls.

“Collectively, these data suggest that although SIRT used in conjunction with systemic chemotherapy provides prolonged control of evident liver disease, this is insufficient to influence PFS at any site”, the researchers write.

The lack of improvement in PFS at all sites may also be related to the unexpectedly high proportion of participants with an intact primary tumour, believed to be a poor prognostic indicator, they add.

The researchers report treatment-emergent adverse events of grade 3 or above in 85.4% of SIRT-treated patients and 73.3% of controls, with a significantly higher rate of thrombocytopenia in those given SIRT (9.8 vs 2.6%).

SIRT-specific side effects were thought to include grade 3 or worse duodenal ulcer in eight of the nine affected patients, ascites in seven, and hepatic failure and radiation hepatitis in three and two patients, respectively.

“The addition of SIRT did not adversely affect the delivery of chemotherapy, and the [adverse event] profile was anticipated and manageable”, the team adds.


van Hazel GA, Heinemann V, Sharma NK, et al. SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol 2016; Advance online publication 22 February. doi: 10.1200/JCO.2015.66.1181

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