Approval of Ziv-aflibercept for Metastatic Colorectal Cancer

On August 3, 2012, the US Food and Drug Administration (FDA) approved ziv-aflibercept (Zaltrap, Sanofi US Inc) for use in combination with FOLFIRI (5-fluorouracil, leuco - vorin, and irinotecan) for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing chemotherapy regimen. Ziv-aflibercept, which was previously known as aflibercept, is an angiogenesis inhibitor that inhibits the blood supply to tumors.

The FDA approval was based on the results of a phase 3 trial of 1226 patients with mCRC whose cancer had progressed during or within 6 months of having received oxaliplatin- based combination chemotherapy, with or without prior bevacizumab. Patients were randomized to receive FOLFIRI with either ziv-aflibercept or placebo. Patients in the trial received treatment until their cancer progressed or side effects became unacceptable.

The primary efficacy end point was overall survival. Patients who received FOLFIRI with ziv-aflibercept had a median overall survival of 13.5 months compared with 12.06 months for patients who received FOLFIRI with placebo. Median progression-free survival for patients in the FOLFIRI with ziv-aflibercept arm was 6.9 months compared with 4.7 months for patients in the FOLFIRI with placebo arm. A reduction in tumor size occurred in 20% of patients who received the FOLFIRI with ziv-aflibercept combination versus 11% for those who received FOLFIRI with placebo.

Ziv-aflibercept was approved with a Boxed Warning alerting patients and healthcare professionals that the drug can cause severe and sometimes fatal bleeding, including gastrointestinal bleeding, and the development of holes in the gastrointestinal tract. Ziv-aflibercept can also make it more difficult for wounds to heal.

The most common side effects observed in patients receiving FOLFIRI with ziv-aflibercept 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.