Sanofi has announced detailed results from the pivotal phase III VELOUR study evaluating ZALTRAP (aflibercept) injection for intravenous infusion for the treatment of patients with previously treated metastatic colorectal cancer. The results were published in the Journal of Clinical Oncology (JCO).
ZALTRAP is a recombinant fusion protein that binds to Vascular Endothelial Growth Factor (VEGF)-A, VEGF-B, and placental growth factor (PlGF). In the VELOUR trial evaluating metastatic colorectal cancer patients previously treated with an oxaliplatin-containing regimen, ZALTRAP in combination with the FOLFIRI chemotherapy regimen (5-fluorouracil, leucovorin, irinotecan) showed a statistically significant improvement in overall survival, progression-free survival, and the overall tumour response rate versus placebo plus FOLFIRI.
“We want to express our appreciation to the authors and the editorial board of the JCO for publishing the results of the VELOUR trial,” said Debasish Roychowdhury, senior vice president and head of Sanofi Oncology. “The scrutiny of the FDA review and peer review processes should provide physicians confidence in the results of VELOUR, as they make important decisions for their patients.”
The VELOUR data supported the regulatory approval of ZALTRAP by the US Food and Drug Administration (FDA) on August 3, 2012 after a Priority Review. In the US, ZALTRAP is approved with the US proper name ziv-aflibercept for use in combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. ZALTRAP is under review at the European Medicines Agency and other regulatory agencies worldwide.
The VELOUR trial showed that in patients previously treated with an oxaliplatin-containing regimen, adding ZALTRAP to FOLFIRI significantly improved median survival from 12.06 months to 13.50 months (HR=0.817 (95% CI 0.714 to 0.935; p=0.0032), an 18 per cent relative risk reduction. A significant improvement in progression-free survival from 4.67 months to 6.90 months (HR=0.758 95 per cent CI 0.661 to 0.869; p=0.00007), a 24 per cent relative risk reduction, was also observed. The overall response rate in the ZALTRAP plus FOLFIRI arm was 19.8 per cent vs. 11.1 per cent for FOLFIRI (p=0.0001).
The most common adverse reactions (all grades, >20% incidence) reported at a higher incidence (twp per cent or greater between-arm difference) in the ZALTRAP-FOLFIRI arm, in order of decreasing frequency, were leucopenia, diarrhoea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache. The most common Grade 3-4 adverse reactions (>5 per cent) reported at a higher incidence (two per cent or greater between-arm difference) in the ZALTRAP-FOLFIRI arm, in order of decreasing frequency, were neutropenia, diarrhoea, hypertension, leucopenia, stomatitis, fatigue, proteinuria, and asthenia.
The phase III VELOUR study was a multinational, randomized, double-blind trial comparing FOLFIRI in combination with either ZALTRAP or placebo in the treatment of patients with metastatic colorectal cancer (mCRC). The study randomized 1,226 patients with mCRC who previously had been treated with an oxaliplatin-containing regimen. The primary endpoint was an improvement in overall survival. Secondary endpoints included progression-free survival, overall response rate, and safety.
ZALTRAP is a recombinant fusion protein that acts as a soluble receptor that binds to Vascular Endothelial Growth Factor-A (VEGF-A), VEGF-B and placental growth factor (PIGF). Under the terms of their collaboration agreement, Sanofi and Regeneron share equally the global profits of ZALTRAP after Regeneron’s obligation to repay its share of development expenses. In the US, ZALTRAP is a registered trademark of Regeneron Pharmaceuticals, Inc.
Worldwide, colorectal cancer is the third most commonly diagnosed cancer in males and the second most in females, with more than 1.2 million new cases diagnosed in 2008.
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