NEWS

FDA Panel Recommends Two New Cancer Drugs for Approval

Joel B. Finkelstein

The U.S. Food and Drug Administration in January approved the drug Femara for first-line treatment of advanced breast cancer. The approval of the aromatase inhibitor was based on the recommendations of the agency’s panel of cancer experts.



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Femara (letrozole tablets) is now an option for postmenopausal women diagnosed with advanced breast cancer. The panel’s recommendation was based on a multinational clinical trial of 916 women. All the women had either hormone-receptor–positive disease or disease of unknown receptor status that could not be treated with surgery or radiation.

The study showed that patients on Femara had an average period of more than 9 months before disease progression compared with about 6 months for patients on tamoxifen. Overall response rates were higher with Femara (30%) than with tamoxifen (20%) although duration of response was similar between the two drugs, according to Femara’s maker, Novartis Oncology, East Hanover, N.J.

Side effects with Femara were very similar to those seen with tamoxifen, including a 1% to 2% incidence each of peripheral thromboembolic, cardiovascular, and cerebrovascular events. There were also a few cases of fractures and ocular problems, but no cases of endometrial cancer in patients who received Femara.

Femara works by binding with aromatase, the enzyme that catalyzes the conversion of male sex hormones into estrogen. This has the effect of lowering the amount of estrogen circulating in the bloodstream through a different mechanism than tamoxifen.

In December hearings, FDA’s Oncologic Drug Advisory Committee also recommended approval of a new monoclonal antibody for chronic lymphocytic leukemia and rejected an interleukin 2 adjunct for treating advanced melanoma that has spread to the liver.

The panel recommended accelerated approval of Campath (alemtuzumab), a humanized monoclonal antibody for patients with chronic lymphocytic leukemia who have been treated with alkylating agents and have failed fludarabine therapy. Currently, alkylating agents are first-line therapy and fludarabine is second-line therapy. Campath would become the only FDA-approved third-line option. At press time, the FDA had not yet given its final approval of Campath, but the FDA usually follows the advice of its expert panels.

Study findings presented to the committee showed that of 93 patients, 33% experienced a 50% reduction in disease burden while 2% of patients had a complete response, defined as nondetectable disease. Responses to therapy lasted about 7 months on average, according to Millennium Pharmaceuticals of Cambridge, Mass.

These findings were supported by two smaller studies that also showed about a 30% overall response rate. However, all three studies were single-arm trials lacking controls and making it difficult to fully assess efficacy and safety.

Treatment with Campath, which is given as an infusion, was associated with infusional toxicity in 90% of patients with a total of 13% being severe cases. Patients also experienced infections and hematological toxicities. Forty-seven percent of patients had to stop taking the therapy for a few days to a week or more and 24% discontinued the therapy altogether due to side effects.

Campath is believed to work by targeting the CD52 antigen present on B and T lymphocytes, inducing complement fixation, cell-mediated cytotoxicity, and apoptosis in these cells. Because bone marrow progenitor cells don’t carry this antigen, the drug should not affect them.

The panel’s recommendation for accelerated approval carries the requirement that the company continue to study Campath in the clinical trial setting even after marketing approval.

ODAC also heard testimony on Maxim Pharmaceuticals’ application for Maxamine, a histamine hydrocloride injection for adjunctive use with interleukin 2 in advanced melanoma that has metastasized to the liver. However, the panel recommended that the application be rejected.

The San Diego-based company reported that survival and response rates were not significantly different between the patients who received Maxamine and those who received interleukin 2 alone. However, in a subgroup of patients with liver metastasis, the company discovered that patients who received the adjunctive therapy did survive longer (9 months vs. 5 months) and had a higher response rate (4% vs. 0%).



             
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