Adding bevacizumab to chemotherapy increases resectability of colorectal liver metastases
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The addition of bevacizumab to modfied FOLFOX6 improved liver metastases resection rates and survival outcomes among certain patients with colorectal liver metastases, according to study results published in Journal of Clinical Oncology.
“To our knowledge, this is the rst randomized controlled trial to test whether the introduction of bevacizumab [Avastin, Genentech] added to chemotherapy (doublet or triplet) will increase the resection rate of liver metastases for patients with RAS-mutant colorectal liver metastases,” Wentao Tang, MD, clinical researcher in the department of general surgery at Zhongshan Hospital in Shanghai, and colleagues wrote. “This study confirms that bevacizumab improves R0 resection rate of liver metastases, PFS and OS when combined with [modified FOLFOX6] for patients with RAS-mutant, initially unresectable colorectal liver metastases. The significant benefit of liver metastases resection rates in the bevacizumab-containing arm was consistent among subgroups of sidedness and primary tumor status.”
Molecule-targeted drugs in combination with oxaliplatin- or irinotecan-based combination chemotherapy have been shown to downsize liver metastases and facilitate secondary resection for patients with colorectal liver metastases.
Bevacizumab, a recombinant humanized monoclonal antibody targeting VEGF, has prolonged survival as first-line treatment of metastatic colorectal cancer when combined with bolus fluorouracil and irinotecan. However, the efficacy of bevacizumab among patients with RAS mutations remained unclear, according to researchers.
Tang and colleagues conducted the randomized BECOME trial to evaluate the effects of bevacizumab added to modified uorouracil, leucovorin and oxaliplatin (mFOLFOX6) as first-line treatment of RAS-mutant unresectable colorectal liver metastases.
The researchers randomly assigned 241 patients with these metastases to bevacizumab plus mFOLFOX6 (n = 121; median age, 58 years; 65.3% men) or mFOLFOX6 alone (n = 120; median age, 59 years; 66.7% men).
The actual rate of patients converted to R0 resection for liver metastases served as the primary endpoint. Tumor response, survival and toxicity served as secondary endpoints.
Median follow-up was 37 months.
Results showed higher R0 resection rates for liver metastases in the bevacizumab group compared with the mFOLFOX6-alone group (22.3% vs. 5.8%; P < .01).
Patients who received the combination had higher objective response rates (54.5% vs. 36.7%; P < .01) and longer median PFS (9.5 months vs. 5.6 months; P < .01) and median OS (25.7 months vs. 20.5 months; P = .03) than those who received mFOLFOX6 alone.
Researchers observed more frequent incidence of proteinuria (9.9% vs. 3.3%; P = .04) and hypertension (8.3% vs. 2.5%; P < .05) among patients who received bevacizumab vs. mFOLFOX6 alone.
The study’s single-center nature and primary endpoint — conversional resection rate, which a surrogate for long-term outcomes — served as limitations.
“Our study confirmed that for Chinese patients with RAS-mutant, initially unresectable colorectal liver-limited metastases, the addition of bevacizumab to mFOLFOX6 increased radical resections of liver metastases with minimal perioperative complications and prolonged long-term survival,” Tang and colleagues wrote.
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