Selective Internal Radiotherapy Does Not Improve Any-Site but Prolongs Liver-Specific Progression-Free Survival in Metastatic Colorectal Cancer
In the phase III SIRFLOX trial reported in the Journal of Clinical Oncology, van Hazel et al found that adding selective internal radiation therapy with yttrium-90 resin microspheres to FOLFOX (fluorouracil, leucovorin, oxaliplatin) with or without bevacizumab (Avastin) did not improve any-site progression-free survival but delayed progression in the liver in first-line treatment of liver-dominant metastatic colorectal cancer.
Study Details
In the trial, 530 patients with liver metastases with or without limited extrahepatic metastases from 87 sites in Australia, Europe, Israel, New Zealand, and the United States were randomized between October 2006 and April 2013 to receive modified FOLFOX6 with (n = 267) or without selective internal radiation therapy (n = 263) plus or minus bevacizumab. Bevacizumab, given at investigator discretion, was received by 57% and 51% of patients who received randomized treatment in each group. The primary endpoint was progression-free survival at any site in the intent-to-treat population as assessed by independent central review.
Progression-Free Survival
Median progression-free survival at any site was 10.7 months in the selective internal radiation therapy group vs 10.2 months in the control group (hazard ratio [HR] = 0.93, P = .43). Median progression-free survival in the liver on competing risk analysis was 20.5 months vs 12.6 months (HR = 0.69, P = .002). Rates of objective response were 76.4% vs 68.1% at any site (P = .113) and 78.7% vs 68.8% in the liver (P = .042).
Toxicity
Grade ≥ 3 adverse events occurred in 85% vs 73% of patients, with hematologic adverse events being more common (P < .05) in the selective internal radiation therapy group (neutropenia in 41% vs 29%, febrile neutropenia in 6% vs 2%, thrombocytopenia in 10% vs 3%). Known selective internal radiation therapy–associated adverse events included grade 3 gastric or duodenal ulcers in eight patients and grade 4 ulcer in one patient. Serious adverse events occurred in 54% vs 42% of patients (P = .005). Adverse events led to death in nine vs five patients.
The investigators concluded: “The addition of selective internal radiation therapy to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liver-only metastatic colorectal cancer did not improve [progression-free survival] at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies.”
The study was supported by Sirtex Technology.
Guy A. van Hazel, MBBS, of The University of Western Australia, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
