National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
August 7, 2012 • Volume 9 / Number 16

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FDA Update

New Drug Approved for Metastatic Colorectal Cancer

The Food and Drug Administration approved ziv-aflibercept (Zaltrap) for use in combination with the FOLFIRI (leucovorin, fluorouracil, and irinotecan) chemotherapy regimen to treat some adults with colorectal cancer.

The drug is an angiogenesis inhibitor, which means it may prevent the development of tumor blood vessels. It is intended for patients with metastatic colorectal cancer whose tumors are resistant to or have progressed after an oxaliplatin-containing chemotherapy regimen.

“This approval demonstrates the benefits of adding a biological agent, Zaltrap, to a commonly used chemotherapy drug regimen, FOLFIRI,” said Dr. Richard Pazdur of the FDA’s Center for Drug Evaluation and Research in an August 3 news release. “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.”

Ziv-aflibercept was evaluated in a randomized clinical trial of 1,226 patients with metastatic colorectal cancer whose cancers had progressed while they were receiving oxaliplatin-based combination chemotherapy. Participants who had relapsed within 6 months of completing oxaliplatin-based chemotherapy after surgery were also eligible, as were patients who had been treated with bevacizumab. Participants received treatment until their cancer progressed or side effects became unacceptable.

Half of the patients in the trial, called the VELOUR study, were randomly assigned to receive the ziv-aflibercept plus FOLFIRI combination, and the other half to receive FOLFIRI plus placebo. The study was designed to evaluate whether ziv-aflibercept improved overall survival. Patients who received ziv-aflibercept lived an average of 13.5 months, compared with an average of 12 months for those receiving the placebo.

Patients who received aflibercept also had better tumor responses: Tumors shrank in 20 percent of patients in the ziv-aflibercept group versus 11 percent of those in the placebo group.

Ziv-aflibercept also improved progression-free survival. Patients receiving the ziv-aflibercept combination lived without their cancer progressing for an average of 6.9 months, versus 4.7 months for those receiving the placebo.

Ziv-aflibercept was approved with a boxed warning that the drug can cause severe and sometimes fatal bleeding, including gastrointestinal bleeding, and holes in the gastrointestinal tract. The warning also states that the drug can compromise wound healing.

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.

Everolimus Approved for Treating Some Breast Cancers

The Food and Drug Administration (FDA) has approved the drug everolimus (Afinitor) in combination with exemestane (Aromasin) to treat certain postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer.

The treatment is intended for women whose disease has progressed after treatment with letrozole (Femara) or anastrozole (Arimidex), according to a July 20 FDA news release.

Everolimus is also approved for treating some patients with advanced renal cell carcinoma, progressive advanced pancreatic neuroendocrine tumors, or the benign brain tumor called subependymal giant cell astrocytoma.

The new approval was based on a clinical trial that showed a 4.6-month improvement in median time to disease progression or death in women who received everolimus and exemestane compared with women who received exemestane and a placebo.

Everolimus prevents cell proliferation and the formation of tumor blood vessels by inhibiting the mammalian target of rapamycin (mTOR) signaling pathway.

The most common side effects in patients receiving everolimus for breast cancer were mouth ulcers, infections, rash, fatigue, diarrhea, and decreased appetite. The FDA cautioned that patients who are aged 65 and older should be monitored closely because they are more likely to have more serious side effects than younger patients.

Carfilzomib Approved for Advanced Multiple Myeloma

The Food and Drug Administration (FDA) has approved carfilzomib (Kyprolis) to treat patients with multiple myeloma whose disease has progressed after at least two prior therapies, including bortezomib (Velcade) and an agent that modulates the immune system such as thalidomide.

Carfilzomib binds to and inhibits enzymes called proteasomes, which degrade cellular proteins. Inhibiting this process leads to cell death and blocks tumor growth.

The July 20 approval was based on the response rate observed in a single-arm study of 266 patients with multiple myeloma who had received at least two prior therapies. One patient taking carfilzomib had all signs of cancer disappear (complete response) and 60 others saw their tumors shrink (partial response), resulting in an overall response rate of 22.9 percent. The median length of time patients responded to carfilzomib was 7.8 months.

Common side effects (observed in more than 30 percent of patients) included fatigue, nausea, anemia, lower-than-normal numbers of red blood cells or platelets, shortness of breath, diarrhea, and fever. Serious adverse reactions were reported in 45 percent of patients. The most common of these were pneumonia, acute kidney failure, fever, and congestive heart failure. The risk of peripheral neuropathy is less with carfilzomib than with similar drugs already on the market, such as bortezomib.

Carfilzomib was approved through the FDA’s accelerated approval program, which allows the agency to approve a drug based on clinical data demonstrating a drug’s effect on a surrogate endpoint, such as response rate, that is likely to predict its benefit to patients. The manufacturer, Onyx Pharmaceuticals, must submit additional data that confirm the drug’s clinical benefit.

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