FDA Approves Letrozole for Advanced Breast Ca.

BETHESDA, MD. -- Letrozole, an oral estrogen-blocking drug, has been approved as a first-line agent in treating postmenopausal women with advanced breast cancer.

The Food and Drug Administration approved the drug in January for treating hormone receptor--positive or "hormone receptor--unknown" advanced or metastatic breast cancer in this population. Letrozole, an aromatase inhibitor, is the second drug in this class approved as a first-line treatment. In September, the FDA approved anastrozole, marketed as Arimidex by AstraZeneca, for postmenopausal women with hormone receptor--positive or hormone receptor--unknown locally advanced or metastatic breast cancer. Like letrozole, anastrozole has been shown to be as effective or more effective than the antiestrogen tamoxifen in treating this population.

In December, the FDA's Oncology Drugs Advisory Committee had unanimously recommended that letrozole be approved for this indication based on the results of a multinational study that compared letrozole with tamoxifen. The median time to disease progression, the primary end point of the study was 3 months longer among patients who were treated with letrozole- a highly significant difference.

The panel unanimously agreed that the data showed the drug was effective for the "initial hormone treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer." Letrozole is "at least equivalent and quite possibly superior" to tamoxifen, said panelist Dr. George Sledge, an oncologist and professor of medicine at Indiana University, Indianapolis.

Letrozole, marketed as Femara by Novartis Pharmaceuticals Corp., was approved in the United States in 1997 as a second-line therapy for treating advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Letrozole is one of several nonsteroidal aromatase inhibitors on the market. These drugs, which are established second-line treatments of advanced breast cancer, block the biosynthesis of estrogen by binding to the enzyme aromatase and blocking it from converting adrenal androgens to estrogen in tissues.

Dr. Sledge said that the clinical experience of physicians who take care of women with breast cancer "is that the aromatase inhibitors in general and letrozole in particular are safe and well tolerated."

At the meeting, Novartis presented data from a study of more than 900 postmenopausal women with locally advanced, recurrent, or metastatic breast cancer.