The FDA has approved ziv-aflibercept (Zaltrap) for use in combination with a FOLFIRI (leucovorin, fluorouracil, irinotecan) chemotherapy regimen to treat adults with colorectal cancer. Ziv-aflibercept is an angiogenesis inhibitor that inhibits the blood supply to tumors. It is intended for patients whose cancer has become metastatic and whose tumors are resistant to or progressed after an oxaliplatin-containing chemotherapy regimen.
Ziv-aflibercept’s safety and effectiveness was 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 6 months after receiving oxaliplatin-based combination chemotherapy for adjuvant treatment. Participants received treatment until their cancer progressed or side effects became unacceptable.
The study was designed to measure overall survival, or the length of time a patient lived. Patients who were assigned to receive the ziv-aflibercept–plus-FOLFIRI combination lived an average of 13.5 months compared to an average of 12 months for those receiving FOLFIRI plus placebo. A reduction in tumor size occurred in 20% of patients receiving the ziv-aflibercept–plus-FOLFIRI combination vs 11% for those receiving FOLFIRI plus placebo.
In addition, the clinical trial demonstrated an improvement in progression-free survival, or the time a patient lived without the cancer progressing. The progression-free survival for patients receiving ziv-aflibercept plus FOLFIRI was 6.9 months compared with 4.7 months for those receiving FOLFIRI plus placebo.
Ziv-aflibercept is being approved with a Boxed Warning stating that the drug can cause severe and sometimes fatal bleeding, including gastrointestinal bleeding, and the development of holes in the gastrointestinal tract. The new agent can also make it more difficult for wounds to heal.
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. ■