David H. Ilson, MD, PhD reviewing van Hazel GA et al. J Clin Oncol 2016 Feb 22.
Adding liver-directed SIRT to chemotherapy fails to improve overall progression-free survival.
Systemic chemotherapy has improved survival in metastatic colorectal cancer. However, a substantial minority of patients have liver-predominant metastases. Whether liver-directed therapy should be part of the treatment strategy is the subject of ongoing debate. Now, investigators have conducted an industry-sponsored, multicenter, randomized phase III trial (SIRFLOX) to determine the potential benefit of adding liver-directed selective internal radiation therapy (SIRT) in previously untreated patients with liver-predominant metastatic disease.
A total of 530 patients were randomized to receive mFOLFOX6 (modified fluorouracil, leucovorin, and oxaliplatin) alone or sequenced with SIRT using yttrium-90 resin microspheres delivered by intrahepatic infusion. Most patients in the SIRT and chemotherapy-alone arms had colonic primaries (72%–80%), most had ≤25% liver involvement (69%–73%), many had extrahepatic disease (40%), and a minority had received prior adjuvant chemotherapy (5%–6%); about half in each arm were allowed to receive bevacizumab (47%–55%).
Progression-free survival (PFS; the primary trial endpoint) was not improved with SIRT plus chemotherapy versus chemotherapy alone (10.7 and 10.2 months, respectively), although PFS in the liver was improved with SIRT (20.5 vs. 12.6 months; P=0.002). Overall tumor response rates were similar with or without SIRT (76% and 68%, respectively), although response in the liver was improved with SIRT (79% vs. 69%; P=0.042). The rate of serious adverse events was higher with SIRT (54% vs. 42%; P=0.005). The rate of grade 5 adverse events was numerically higher with SIRT (9 vs. 5 patients; 4% vs. 2%), including 3 cases overall of hepatic failure.
Citation(s):
van Hazel GA 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 Feb 22; [e-pub].
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