Advisers recommend approval of new breast cancer treatment - Femara by Novartis

LAURAN NEERGAARD / AP 13dec00

BETHESDA, Md. -- A large international study found a drug called Femara may fight advanced breast cancer a little better than today's top treatment, prompting government advisers Wednesday to recommend approving the pill as a first-line option.

The move signals a possible shift in care of late-stage breast cancer, as a new class of drugs becomes poised to challenge the longtime standard therapy, the drug tamoxifen.

The new study provides ``fairly compelling data'' that Femara ``is at least equivalent to tamoxifen and possibly superior,'' said Dr. George Sledge, an Indiana University cancer expert and adviser to the Food and Drug Administration.

In a study of 907 postmenopausal women with advanced breast cancer, Femara provided a median of 3.6 more months before tumors worsened than did tamoxifen. That is a meaningful amount of time for this late-stage cancer, letting women postpone consideration of more toxic chemotherapy, experts note.

Overall, the risk of disease worsening was 30 percent less among Femara patients than tamoxifen patients, FDA medical officers concluded. The study is continuing to see if Femara or tamoxifen helped women live longer.

Still, the FDA's scientific advisers voted unanimously Wednesday that Femara, known chemically as letrozole, should be approved as a first-line therapy for metastatic breast cancer, the kind that has spread through the body.

Novartis Pharmaceuticals Corp. already sells Femara as a backup for when tamoxifen fails. But if the FDA upgrades the drug, Femara will be poised to challenge tamoxifen and a second drug, Arimidex, in hopes of becoming the most used therapy for these very sick women.

The FDA is not bound by its advisers' recommendations but typically follows them.

Estrogen fuels the growth of about half of all breast cancers, especially those in older women. Tamoxifen, the top hormonal treatment for estrogen-fueled tumors, is given to almost all such U.S. patients after surgery to help prevent breast tumors from returning.

In addition, when breast cancer returns and spreads, tamoxifen is the top treatment to stall tumor growth and buy women some time. It prevents estrogen from linking up to a receptor on the surface of cancer cells.

At issue now is a new class of cancer drugs called aromatase inhibitors, which work by blocking production of estrogen. They are used mostly when tamoxifen fails.

One drug, AstraZeneca's Arimidex, recently won approval as a first-line option for advanced cancer when studies found it equivalent to tamoxifen, FDA said. Now the larger Novartis-funded study suggests competitor Femara actually might be more effective than tamoxifen for metastatic disease.

While it is unclear if one aromatase inhibitor is better than the other, studies of both drugs against advanced cancer ``suggest standards of care may be shifting now to use this class of compounds first,'' said FDA adviser Dr. Kathy Albain, a Loyola University oncologist.

But there is no data to show if aromatase inhibitors should be used against earlier stage cancer, she said. Those studies are ongoing.

Some FDA advisers did question the Femara study because most of the patients were from Russia and China; only 100 Americans were included. FDA officials visited Russia to check on data and say they have no reason to believe results from other countries skewed the study.

In fact, one FDA adviser said the study shows Americans may benefit more from Femara because they are more likely than women abroad to have used tamoxifen after initial cancer surgery.

Thus, when their cancer returned and spread years later, a new round of tamoxifen was far less likely to help them -- 8 percent of such patients responded to tamoxifen vs. 29 percent who responded to Femara.

• Food and Drug Administration site: http://www.fda.gov/
• Novartis Pharmaceuticals Corp. information on Femara: http://www.pharma.us.novartis.com/product/pi/pdf/femara.pdf
• National Cancer Institute information on breast cancer: http://cancernet.nci.nih.gov/cancer--types/breast--cancer.shtml