Zaltrap: A New Colorectal Drug Approved by the FDA

More new drugs for the war against cancer! Just in the past year there has been so much new activity in oncology medications. Last year we had two new drugs for metastatic melanoma: Zelboraf (vemurafenib) and Yervoy (ipilimumab). Now this year we have possibly two new chemotherapy drugs for metastatic colon cancer: Zaltrap (ziv-aflibercept) which was just approved by the United States Food and Drug Administration (FDA) last week and hopefully to be approved later this year another drug named regorafenib (an orally active angiogenic inhibitor).

Zaltrap is an angiogenesis inhibitor and akin to Avastin (bevacuzimab). It is administered intravenously and provides a wider mechanism of action by fusing with more vascular endothelial growth factor (VEGF) receptors than Avastin does. In the scientific realm, it is lovingly being referred to as the "VEGF Trap."

The approval for use was based on the outcome of the phase three VELOUR (Aflibercept Versus Placebo in Metastatic Colorectal Cancer After Failure of an Oxaliplatin-Based Regimen) trial.

• Out of the 1,226 patients who participated in this trial, there was an increase in response rate to 20 percent, up from 10 percent when compared to FOLFIRI (folinic acid, fluorouracil, and irinotecan) with placebo.
• Also seen was a delay in tumor growth and/or progression.
• Tumor size was seen to decrease by 20 percent compared to 11 percent.
• Progression Free Survival at 6.89 months versus 4.7 month.
• Overall survival was 13.5 months versus 12 months.

The new drug is also indicated for second-line use after progression on an oxaliplatin-containing regimen or for tumor-resistant situations. No decisions yet if Zaltrap should replace Avastin in the second-line attempt, that depends on clinical decision making and how the patient is currently doing on Avastin. So likely, we will be seeing metastatic colon cancer patients (if they progress) switch from FOLFOX (folinic acid, fluorouracil, and oxaliplatin) or FOL FOX with Avastin to FOLFIRI with Avastin or Zaltrap.

Side effects seen with Zaltrap include leucopenia, diarrhea, stomatitis, fatigue, an increase in blood pressure, dysgeusia, weight loss, abdominal pain, headache, and proteinuria. There is a black box warning with Zaltrap for gastrointestinal (GI) or fatal bleeding, fistulas in the GI tract, and/or a decrease in wound healing.

This is again another great step for advancements in colon cancer, considering it is still the fourth most common type of cancer and also the fourth leading cause of death in the United States. It is predicted by the National Institute of Health that 143,460 people will be diagnosed with colon cancer this year and out of that group approximately 51,690 will die from the disease.

A form of aflibercept has already been in use as of last year for another condition: as a locally-injectable ophthalmic solution for the treatment of neovascular (wet) age-related macular degeneration, under the name of Eylea. Also, aflibercept has been investigated for prostate cancer, but a large phase three study, known as VENICE, showed no improvement in overall survival yet.

Have you seen Zaltrap used in a clinical trial setting? Do you think your practice/clinic will be quick to adopt this new medication?

References:

• Chustecka, Z. (2012). Aflibercept Approved for Colorectal Cancer in the US. Retrieved from: http://www.medscape.com/viewarticle/768551?src=emailthis.
• Gobel, B.H., Triest-Robertson, S., & Vogel, W.H. (2009). Advanced Oncology Nursing Certification Review and Resource Manual. Oncology Nursing Society. Pittsburgh, Pennsylvania.
• United States Food and Drug Administration (august 3, 2012). FDA approves Zaltrap for metastatic colorectal cancer. Retrieved from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm314372.htm.