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Ziv-Aflibercept gets FDA approval

Ziv-Aflibercept Approved as 2nd line treatment for metastatic CRC  

For the first time in more than five years, the FDA has approved a new drug for certain patients who have metastatic colorectal cancer.

The FDA has approved ZALTRAP® (ziv-aflibercept) to be used with FOLFIRI as a “second-line” treatment for patients with stage IV colorectal cancer whose cancer got worse despite an initial oxaliplatin-based treatment (e.g. FOLFOX). 

Trial evidence

This FDA approval is based on the Phase III VELOUR trial, which studied 1226 patients whose metastatic cancer had progressed during or within six months of receiving the combination chemotherapy FOLFOX, with or without Avastin® (bevacizumab). Patients were randomly assigned to get FOLFIRI alone or FOLFIRI plus Zaltrap. Results showed:

  • Improved overall survival from 12 to 13.5 months
  • Progression-free survival increased from 4.7 to 6.9 months
  • The addition of ziv-aflibercept doubled the response rate from 10% with FOLFIRI up to a 20% response rate when Zaltrap was added.

The study also showed improved response even in the 30 percent of patients who had previously taken Avastin® (bevacuzimab) with FOLFOX.

How it works

Like its cousin Avastin, the new drug Zaltrap is a biologic (targeted) protein that blocks the development of new blood vessels needed by a fast-growing tumor. Zaltrap disguises itself as the receptor, basically setting a trap (hence its name) that captures and blocks three different growth factors (two VEGFs and placental growth factor).

Side effects

Perhaps because it has a broader spectrum of action than Avastin, Zaltrap seems to cause more side effects. The FDA approval comes with a “black box” warning of rare but serious or life-threatening side effects such as severe bleeding, gastrointestinal perforation (a hole in the stomach or intestine), and delayed wound healing. But the most common side effects seen in trials were low white blood cells, diarrhea, high blood pressure, mouth sores, fatigue and muscle weakness.

Further research coming

For this notoriously hard-to-treat cancer, even an improved “mean” survival time (the middle point between shortest and longest response) of just 1.5 months is a significant scientific advance. Plus it gives a second treatment option for people with metastatic colorectal cancer.

Now researchers will carefully study patients who responded particularly well, looking for clues about why, how, and in whom Zaltrap works best. Other researchers with the Phase II AFFIRM clinical trial  are studying whether Zaltrap could be used with FOLFOX as an initial (first-line) treatment for metastatic colorectal cancer.

Other clinical data hints that some patients might benefit from continuing Avastin even if their cancer progresses. Dr. David Kerr, president of the European Society of Medical Oncology, told Medscape that “We will need head-to-head trials to sort out [the] dilemma” of when to keep patients on Avastin or try switching to Zaltrap.

Another new drug in the pipeline for stage IV colorectal cancer this year is the pill Regorafenib. With positive early trial results, the FDA put Regorafenib on the “priority review” list in late June, meaning approval could come later this year.

Patient take-away

The new drug ziv-aflibercept will be commercially available the week of August 20th, the manufacturer told Fight Colorectal Cancer. With FDA approval, this drug should be covered by Medicare and most insurers. Oncologists now can begin considering Zaltrap as an option for some patients with stage IV disease. But it won’t be a simple black-and-white decision.

For example, Dr. John Marshall (head of the Lombardi Comprehensive Cancer Center in Washington DC) described his decision process to  Medscape Medical News :  “If I had a very stable patient with metastatic cancer on frontline therapy with just subtle progression after 12 months, I’d probably keep that patient on bevacizumab (Avastin). However, in a patient who is not having a good response and who has rapidly progressing cancer, I might consider trying ziv-aflibercept as a different approach.”

And people with the wild-type (WT, or nonmutated) KRAS gene have a third option—either Erbitux™ (cetuximab) or Vectibix™ (panitumumab). In July, the FDA approved Erbitux in combination with FOLFIRI for first-line treatment of patients with that type of metastatic colorectal cancer.

So a new drug option for people with stage IV colorectal cancer is great news. But you need to review your specific situation with your doctor—previous treatment and response, plus your general health status and ability to tolerate possible side effects.

If you have questions, call our AnswerLine at 1-877-427-2111.

Sources: Federal Drug Administration, Medscape.

Disclosure: Fight Colorectal Cancer has accepted funding for projects and educational programs from sanofi-aventis, Genentech and Amgen in the form of unrestricted educational grants. Fight Colorectal Cancer has ultimate authority over website content.  Fight Colorectal Cancer Funding Policy and Disclosure.

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