FDA Approves Femara (Letrozole) For First-Line Treatment For Breast Cancer
EAST HANOVER, NJ -- January 11, 2001 -- Novartis Oncology announced that the U.S. Food and Drug Administration has approved Femara® (letrozole tablets) for the first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer. Most postmenopausal women with advanced breast cancer fall into these tumor receptor categories.
Approval of the new indication followed a priority review by the FDA and a unanimous recommendation from the FDA's Oncologic Drugs Advisory Committee. The recommendation was based on data from the largest single 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. Tamoxifen has traditionally been the standard of therapy for this indication.
"Femara shows great promise for becoming the new first-line therapy of choice for postmenopausal women with advanced breast cancer," said Robert Smith, MD, South Carolina Oncology Associates and a lead investigator in the first-line study. "It is the first therapy to challenge tamoxifen in multiple endpoints, including time to progression, response rates and overall clinical benefit."
The Phase III trial on which the FDA based its decision 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. Results also indicated significant differences between Femara and tamoxifen with respect to overall tumor response rates (30 percent vs. 20 percent), clinical benefit (49 percent vs. 38 percent) and time to treatment failure (9.1 months vs. 5.7 months / 40 weeks vs. 25 weeks). Femara and tamoxifen were equally well tolerated.
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 breast-conserving surgery. Clinical responses after four months of preoperative therapy were significantly better for Femara than for tamoxifen (55 percent versus 36 percent).
"Novartis is pleased that the FDA has recognized Femara's strong efficacy and safety profile and has deemed it worthy of the first-line indication," said David Epstein, President, Novartis Oncology. "We look forward to soon being able to offer Femara as first-line hormonal therapy all over the world to postmenopausal women with advanced breast cancer."
Femara, an aromatase inhibitor, is a once-a-day oral treatment that was first approved for marketing in 1997 for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. 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.
In postmenopausal women, the primary source of estrogen 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 works by binding to the enzyme aromatase and blocking it from converting adrenal androgens to estrogen in these tissues.
"FDA approval of this new indication means that thousands of postmenopausal women with advanced breast cancer will finally have a more effective hormonal treatment option," said David Parkinson, MD, Vice President, Clinical Research at Novartis Oncology. "Novartis Oncology is proud to be at the forefront of the development of this and other products that can make a significant difference in patients' lives."
Femara is currently available in more than 75 countries worldwide as a treatment for advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Regulatory submissions for the first-line indication have also been filed globally; the drug is also being studied in the adjuvant setting.
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.
Femara is contraindicated in patients with known hypersensitivity to Femara or any of its excipients. Femara is generally well-tolerated. The adverse reactions in the first-line study were generally mild to moderate and were consistent with those seen in the second-line studies. The most commonly reported adverse events for Femara vs. tamoxifen were bone pain (20 percent vs. 18 percent), hot flushes (18 percent vs. 15 percent), back pain (17 percent vs. 17 percent), nausea (15 percent vs. 16 percent), dyspnea or labored breathing (14 percent vs. 15 percent), arthralgia (14 percent vs. 13 percent), fatigue (11 percent vs. 11 percent) and coughing (11 percent vs. 10 percent). |
