The Food and Drug Administration today approved the use of the angiogenesis inhibitor Zaltrap (ziv-aflibercept) for use in combination with FOLFIRI (folinic acid, fluorouracil, and irinotecan) to treat adults with metastatic colorectal cancer that has been resistant to or has progressed after treatment with an oxaliplatin-containing chemotherapy regimen.
“This approval demonstrates the benefits of adding a biological agent, Zaltrap, to a commonly used chemotherapy drug regimen, FOLFIRI,” Richard Pazdur, MD, the FDA's Director of the Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research, said in a statement. “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.”
An FDA news release notes that Zaltrap's safety and effectiveness were evaluated in a randomized clinical study of 1,226 patients with metastatic colorectal cancer whose cancer grew while receiving oxaliplatin-based combination chemotherapy, or whose cancer was removed by surgery but returned within six months after receiving oxaliplatin-based combination chemotherapy for adjuvant treatment. Participants received treatment until their cancer progressed or side effects became unacceptable.
Patients assigned to receive the Zaltrap-plus-FOLFIRI regimen lived an average of 13.5 months compared with an average of 12 months for those receiving FOLFIRI plus placebo. A reduction in tumor size occurred in 20 percent of patients receiving the combination versus 11 percent for those receiving FOLFIRI plus placebo.
There was also an improvement in progression-free survival, which was 6.9 months for those receiving Zaltrap plus FOLFIRI, vs. 4.7 months for those receiving FOLFIRI plus placebo.
Zaltrap, made by Sanofi-Aventis, was approved with a Boxed Warning that the drug can cause severe and sometimes fatal bleeding, including gastrointestinal bleeding, and the development of holes in the GI tract. The drug can also make it more difficult for wounds to heal.
The most common side effects observed in patients receiving Zaltrap plus FOLFIRI were decreased white blood cell count, diarrhea, mouth ulcers, fatigue, high blood pressure, increased protein in the urine, weight loss, decreased appetite, abdominal pain, and headache.