Researchers affiliated with the BIG-98 trial comparing Femara® (letrozole) to Nolvadex® (tamoxifen) have reported that longer follow-up confirms the superiority of Femara in  postmenopausal women with early, hormone-positive breast cancer. The details of this follow-up study were presented at the 2006 annual European Society for Medical Oncology (ESMO) meeting in Istanbul in October.

Femara is an aromatase agent that is approved for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced breast cancer; metastatic breast cancer; advanced breast cancer in postmenopausal women with disease progression following anti-estrogen therapy; and as neo-adjuvant therapy. It is also approved for extended adjuvant therapy in early breast cancer, following 5 years of treatment with Nolvadex, based on phase III clinical trial results. Several clinical trials are ongoing to help elucidate optimal timing and/or sequencing of aromatase agents and Nolvadex in the treatment of hormone-positive women with breast cancer in the adjuvant setting, and it appears that aromatase agents are providing superior results to those of Nolvadex in several settings in the treatment of hormone-positive breast cancer.

The BIG I-98 trial is a phase III, double-blind, controlled clinical trial conducted in 27 countries involving 8,000 postmenopausal women with early hormone positive breast cancer. Patients were randomized to receive hormone therapy within 5 years of surgery. The randomization included the following: Nolvadex for 5 years, Femara for 5 years, Nolvadex for 2 years followed by Femara for 3 years, and Femara for 2 years followed by Nolvadex for 3 years. The interim results of this trial with a 26-month follow-up were published in the New England Journal of Medicine in December 2005 (see first item in related news). Results at a follow-up of two years indicated that Femara significantly reduced the risk of cancer recurrence compared to Nolvadex.

The current analysis includes approximately 5,000 women and compares the two groups who were assigned to receive Nolvadex initially. Now, researchers have presented results from a four-year follow-up of these patients. Their findings include the following:

• Patients treated with Femara had an 18% reduced risk of a cancer recurrence.
• Patients treated with Femara had a 19% reduced risk of distant spread.
• Node-Negative patients had a 12% decreased risk of a cancer recurrence, a risk reduction that was not demonstrated at the two-year follow-up of this trial.
• Women who had received prior chemotherapy had a 26% reduced risk of a cancer recurrence if they were treated with Femara. 
• Women whose cancer had spread to the lymph nodes had a 23% reduced risk of a cancer recurrence if they were treated with Femara.
• There was no increase in side effects with longer use of Femara.

The researchers concluded that longer follow-up results indicate that Femara continues to be more effective than Nolvadex in postmenopausal women with early, hormone-positive breast cancer.

Comments:  It would appear that either Arimidex or Femara has supplanted Nolvadex for first-line hormonal treatment of breast cancer.

Reference: Coates A, Keshaviah A, Thurlimann B, et al. Five Years of Continuous Letrozole versus Tamoxifen as Adjuvant Therapy for Postmenopausal Women with Endocrine-Responsive Breast Cancer: Further Analyses and Update of BIG 1-98. Proceedings from the 2006 annual meeting of the European Society for Medical Oncology. Istanbul, Turkey. Annals of Oncology. 2006;17 (supplement 9):iX93, Abstract #2410.

Related News   

Femara® More Effective Than Nolvadex® for Early Breast Cancer (01/03/2006)

Delayed Administration of Femara® After 5 Years of Nolvadex® Reduces Recurrence Rates in Patients with Hormone-Positive Localized Breast Cancer (12/21/2005)

Updated Results: Femara® Following Nolvadex® in Breast Cancer (9/15/2005)

Adjuvant Femara® Superior to Nolvadex® for Hormone Responsive Breast Cancer (6/15/2005)

Interim Results Demonstrate Improved Disease-Free Survival with Femara® Over Nolvadex® For Adjuvant Breast Therapy (2/11/2005)

Femara® Approved for Early Breast Cancer (11/30/2004)