Adding First-Line Selective Internal Radiotherapy to Chemotherapy in Patients With Liver Metastases From Colorectal Cancer
A meta-analysis of three randomized trials (FOXFIRE, SIRFLOX, and FOXFIRE-Global) indicates no overall survival benefit of adding first-line selective internal radiotherapy to chemotherapy in patients with liver metastases from colorectal cancer. The findings were reported by Wasan et al in The Lancet Oncology.
Study Details
The FOXFIRE, SIRFLOX, and FOXFIRE-Global trials were designed for combined analysis of overall survival. In each of the open-label trials, patients with liver-only or liver-dominant metastases from colorectal cancer with or without the primary tumor in situ were randomized to receive FOLFOX (oxaliplatin, fluorouracil, leucovorin) regimens with or without selective internal radiotherapy using yttrium-90 resin microspheres. The liver metastases were not suitable for curative resection or ablation.
The primary endpoint was overall survival analyzed in the intention-to-treat population using a two-stage meta-analysis of pooled individual patient data. All three trials had completed 2 years of follow-up at the time of analysis.
Survival
A total of 1,103 patients were randomized between October 2006 and December 2014 to receive FOLFOX plus selective internal radiotherapy (n = 554) or FOLFOX alone (n = 549). Median follow-up was 43.3 months.
Overall, death occurred in 78% of the FOLFOX plus selective internal radiotherapy group and 75% of the FOLFOX-alone group, with no difference in overall survival (hazard ratio [HR] = 1.04, P = .61). Median overall survival was 22.6 months vs 23.3 months. Median progression-free survival was 11.0 vs 10.3 months (HR = 0.90, P = .11).
Adverse Events
The most common grade 3 or 4 adverse event was neutropenia, observed in 37% of the FOLFOX plus selective internal radiotherapy group vs 24% of the FOLFOX group. Serious adverse events occurred in 54% vs 43% of patients. Adverse events led to death in 10 patients in the FOLFOX plus selective internal radiotherapy group and 11 patients in the FOLFOX-alone group, with death considered related to treatment in 8 patients and 3 patients, respectively.
The investigators concluded: “Addition of [selective internal radiotherapy] to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of [selective internal radiotherapy] in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of [selective internal radiotherapy] in metastatic colorectal cancer, careful patient selection and studies investigating the role of [selective internal radiotherapy] as consolidation therapy after chemotherapy are needed.”
The study was supported by the Bobby Moore Fund of Cancer Research UK and Sirtex Medical.
Ricky Sharma, PhD, of the University College London Cancer Institute, is the corresponding author of The Lancet Oncology article.
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