Novartis Oncology announced that the Oncologic Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) today recommended approval of Femara(R) (letrozole tablets) as first-line hormonal treatment for advanced breast cancer in postmenopausal women.

The recommendation was based on data from the largest study ever to evaluate a hormonal therapy in this setting. The study found that Femara was significantly more effective than tamoxifen in multiple efficacy endpoints. At present, tamoxifen is the standard of therapy for this indication.

"We are pleased with the ODAC recommendations and with the potential Femara may further offer the oncology community," said David Epstein, President, Novartis Oncology. "Discovered and developed by Novartis, Femara represents our organization's mission of delivering oncology products that help make a meaningful difference in patients' lives."

Femara, an aromatase inhibitor, is a once-a-day oral treatment currently indicated for treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Femara received FDA approval for its current indication in 1997.

The FDA generally follows the recommendations of its Advisory Committees, although it is not obliged to do so. In July 2000, Novartis submitted a supplemental New Drug Application (sNDA) for first-line therapy in advanced breast cancer and, in August 2000, the sNDA received a priority review designation from the FDA.

"Novartis is pleased that the FDA Advisory Board has recognized the very favorable safety and efficacy profile of Femara and has recommended its approval as first-line hormonal therapy for the thousands of postmenopausal women with advanced breast cancer," said David Parkinson, MD, Vice President, Clinical Research at Novartis Oncology. "Femara's superiority to tamoxifen based on these studies means these women may soon have a more effective treatment. Novartis will continue to work closely with the FDA throughout the approval process and looks forward to offering Femara for this new indication."

Study Involved More Than 900 Women

The Phase III trial on which the Advisory Committee based its recommendation was a head-to-head, randomized, double-blind multi-center trial comparing the use of Femara versus tamoxifen in more than 900 postmenopausal women who had locally advanced (stage IIIB) disease, metastatic breast cancer, or recurrences not amenable to treatment with surgery or radiotherapy.

The study demonstrated that Femara delays progression of advanced breast cancer for 9.4 months, as compared to 6.0 months for tamoxifen (41 weeks vs. 26 weeks). Results also indicated significant differences between Femara and tamoxifen with respect to overall tumor response rates (30% vs. 20%), clinical benefit (49% vs. 38%) and time to treatment failure (9.1 months vs. 5.7 months / 40 weeks vs. 25 weeks). Femara and tamoxifen were equally well tolerated.

Additional Study

Supporting the filing was a Phase III randomized controlled trial of 324 postmenopausal women with large localized or locally advanced breast cancer tumors who were given Femara or tamoxifen as pre-operative treatment to reduce tumor size before surgery. Clinical responses after four months of preoperative therapy were significantly better for Femara than for tamoxifen (55% versus 36%).

"The availability of letrozole as a first-line option could lead us to seriously consider changing the treatment paradigm for advanced breast cancer in postmenopausal women. It is the first therapy to consistently challenge tamoxifen in multiple endpoints, including response rates, time to progression and clinical benefit," said Matthew Ellis, MD, Ph.D., FRCP, Clinical Director, Duke Breast Cancer Program, Duke University Medical Center. Dr. Ellis is also a Femara investigator.

Advanced Breast Cancer

More than 120,000 women in the United States have advanced breast cancer, the second leading cause of cancer death among American women. Approximately half of the 182,000 newly diagnosed cases of breast cancer each year are already in an advanced stage when they are detected.

The primary source of estrogen in postmenopausal women is from fat, liver, muscle, and breast tissue, through a process that turns adrenal androgens into estrogen, which stimulates the growth of certain hormone-dependent cancer cells. A breast tumor itself also may generate estrogen.

Femara, an aromatase inhibitor, binds to the enzyme aromatase and blocks it from converting adrenal androgens to estrogen in these tissues.

Contraindications and adverse effects

Femara is contraindicated in patients with known hypersensitivity to Femara or any of its excipients. Most commonly reported adverse effects with Femara in the second-line trials have been musculoskeletal pain (21%), nausea (13%), headache (9%), arthralgia or joint pain (8%), fatigue (8%), vomiting (7%), and dyspnea or labored breathing (7%).