New Drug Approved for Metastatic Colorectal Cancer: ziv-aflibercept (Zaltrap)
New Drug Approved for Metastatic Colorectal CancerThe Food and Drug Administration approved ziv-aflibercept (Zaltrap) for use in combination with the FOLFIRI (leucovorin, fluorouracil, and irinotecan) chemotherapy regimen to treat some adults with colorectal cancer.
The drug is an angiogenesis inhibitor, which means it may prevent the development of tumor blood vessels. It is intended for patients with metastatic colorectal cancer whose tumors are resistant to or have progressed after an oxaliplatin-containing chemotherapy regimen.
“This approval demonstrates the benefits of adding a biological agent, Zaltrap, to a commonly used chemotherapy drug regimen, FOLFIRI,” said Dr. Richard Pazdur of the FDA’s Center for Drug Evaluation and Research in an August 3 news release. “An improvement in median survival time was noted with the addition of Zaltrap to FOLFIRI, accompanied by an improvement in response rate and a delay in tumor progression and growth.”
Ziv-aflibercept was evaluated in a randomized clinical trial of 1,226 patients with metastatic colorectal cancer whose cancers had progressed while they were receiving oxaliplatin-based combination chemotherapy. Participants who had relapsed within 6 months of completing oxaliplatin-based chemotherapy after surgery were also eligible, as were patients who had been treated with bevacizumab. Participants received treatment until their cancer progressed or side effects became unacceptable.
Half of the patients in the trial, called the VELOUR study, were randomly assigned to receive the ziv-aflibercept plus FOLFIRI combination, and the other half to receive FOLFIRI plus placebo. The study was designed to evaluate whether ziv-aflibercept improved overall survival. Patients who received ziv-aflibercept lived an average of 13.5 months, compared with an average of 12 months for those receiving the placebo.
Patients who received aflibercept also had better tumor responses: Tumors shrank in 20 percent of patients in the ziv-aflibercept group versus 11 percent of those in the placebo group.
Ziv-aflibercept also improved progression-free survival. Patients receiving the ziv-aflibercept combination lived without their cancer progressing for an average of 6.9 months, versus 4.7 months for those receiving the placebo.
Ziv-aflibercept was approved with a boxed warning that the drug can cause severe and sometimes fatal bleeding, including gastrointestinal bleeding, and holes in the gastrointestinal tract. The warning also states that the drug can compromise wound healing.
The most common side effects observed in patients receiving ziv-aflibercept plus FOLFIRI were decreased white blood cell count, diarrhea, mouth ulcers, fatigue, high blood pressure, increased amount of protein in the urine, weight loss, decreased appetite, abdominal pain, and headache.