Metastatic colorectal cancer treatment is approved

August 6, 2012
Formulary staff
Formulary staff

FDA has approved ziv-aflibercept (Zaltrap, Sanofi and Regeneron Pharmaceuticals) injection for intravenous infusion, in combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), for patients with metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin-containing regimen.

FDA has approved ziv-aflibercept (Zaltrap, Sanofi and Regeneron Pharmaceuticals) injection for intravenous infusion, 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.

Colorectal cancer is one of the deadliest cancers and is responsible for more than half a million deaths globally each year, according to a Sanofi Oncology press release.

“Patients who are resistant to or progress following oxaliplatin-containing chemotherapy have limited treatment options,” said Oncology spokesperson Lauren Musto. “Zaltrap offers a new treatment option for this difficult-to-manage disease.”

Ziv-aflibercept injection for intravenous infusion is a recombinant fusion protein, which acts as a soluble receptor that binds to vascular endothelial growth factor-A (VEGF-A), VEGF-B, and placental growth factor. Inhibition of these factors can result in decreased neovascularization and decreased vascular permeability. It was approved following a priority review by FDA.

The ziv-aflibercept injection for intravenous infusion approval was based on data from the pivotal phase 3 VELOUR trial, a multinational, randomized, double-blind trial comparing FOLFIRI in combination with either ZALTRAP or placebo in the treatment of patients with mCRC. The study randomized 1,226 patients with mCRC who previously had been treated with an oxaliplatin-containing regimen. Twenty-eight percent of patients in the study received prior bevacizumab therapy. The primary end point was overall survival. Secondary end points included progression-free survival, overall response rate, and safety.

The VELOUR trial showed that adding ziv-aflibercept injection for intravenous infusion to the chemotherapy regimen FOLFIRI significantly improved median survival from 12.06 months to 13.50 months (HR=0.817; 95% CI, 0.714–0.935; P=.0032), an 18% relative risk reduction. A significant improvement in progression-free survival from 4.67 months to 6.90 months (HR=0.758; 95% CI, 0.661–0.869; P=.00007), a 24% relative risk reduction, was also observed. Overall response rate in the Zaltrap plus FOLFIRI arm was 19.8% versus 11.1% for FOLFIRI and placebo (P =.0001).

The most common adverse reactions (all grades, ≥20% incidence) reported at a higher incidence (2% or greater between-arm difference) in the Zaltrap/FOLFIRI arm, in order of decreasing frequency, were leukopenia, diarrhea, neutropenia, proteinuria, increased AST, stomatitis, fatigue, thrombocytopenia, increased ALT, hypertension, decreased weight, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache. The most common Grade 3-4 adverse reactions (≥5%) reported at a higher incidence (2% or greater between-arm difference) in the ziv-aflibercept injection for intravenous infusion/FOLFIRI arm, in order of decreasing frequency, were neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia.