Aflibercept Delivers Positive Results in Colorectal Trial

Aflibercept, an investigational angiogenesis inhibitor, improved overall survival (OS) as a second-line treatment for patients with metastatic colorectal cancer (mCRC) in a multinational, double-blind phase III trial, 2 pharmaceutical companies developing the drug said this week.

As a result of the positive findings, sanofi-aventis and partner Regeneron Pharmaceuticals, Inc said in a joint statement they are moving forward with plans to submit new drug applications to the FDA and the European Medicines Agency during the second half of this year. The trade name for the drug is Zaltrap.

Aflibercept, also known as VEGF Trap, is considered the most promising compound in a relatively new class of soluble vascular endothelial growth factor (VEGF) receptor drugs aimed at disrupting the tumor-promoting process of angiogenesis. (Onco Targets Ther. 2010; 3:69—82). It works by binding VEGF-A, VEGF-B, and placental growth factor, thus preventing these molecules from binding to their native receptors and in the process disrupting angiogenesis.

The 2 companies also are investigating aflibercept in first-line settings, both for patients with mCRC and for patients with hormone-refractory metastatic prostate cancer. In March, the partners reported that the drug did not meet its primary endpoint of OS in the second-line treatment of non-small cell lung cancer.

The positive findings in the colorectal study involve the VELOUR study, which accrued 1226 patients with mCRC who were previously treated with an oxaliplatin-based regimen. The participants were randomized to receive aflibercept in combination with the FOLFIRI (folinic acid [leucovorin], 5-fluorouracil, and irinotecan) chemotherapy regimen or a regimen of FOLFIRI plus placebo.

The drug was administered by intravenous infusion during a 1-hour period. The recommended dose is 2 mg/kg per week, either 4 mg/kg IV every 2 weeks or 6 mg/kg IV every 3 weeks, according to a spokeswoman for sanofi-aventis.

The companies said the most frequent adverse events reported in the aflibercept arm included diarrhea, asthenia/fatigue, stomatitis and ulceration, nausea, infection, hypertension, gastrointestinal and abdominal pains, vomiting, decreased appetite, decreased weight, epistaxis, alopecia, and dysphonia.

No further details about the trial were released; the findings will be submitted for presentation at an upcoming medical meeting.

"These findings are exciting given the limited second-line treatment options for patients with metastatic colorectal cancer," George D. Yancopoulos, MD, PhD, chief scientific officer of Regeneron and president of Regeneron Research Laboratories, said in a press release.

More than 140,000 people in the United States likely will be diagnosed with cancers of the colon and rectum this year, according to the American Cancer Society. Five-year survival rates range from 74% for those diagnosed at an early stage to 6% for those at stage IV, the ACS said.