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Adjuvant Exemestane After Tamoxifen Improves Relapse- and Disease-Free Survival: Presented at SABCS

By Emma Hitt, PhD

SAN ANTONIO, TX -- December 18, 2006 -- Postmenopausal women with hormone receptor-positive breast cancer who received exemestane after 5 years of tamoxifen therapy were 56% less likely to have a relapse of breast cancer than those who received placebo (P = .004), according to new findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-33 study.

Eleftherios P. Mamounas, MD, medical director, Aultman Cancer Center, Canton, Ohio, reported the findings here on December 15^th at the 29^th Annual San Antonio Breast Cancer Symposium (SABCS).

The study included 1,598 patients with clinical stage T1-3, N0-1, M0 breast cancer, who were disease-free after 5 years of tamoxifen. Of 1,577 eligible patients, 52% were node-negative and 49% were younger than 60 years. After 5 years of tamoxifen, patients were randomized to receive 5 years (amended from 2 years in 2002) of either exemestane or placebo.

Accrual of the trial was stopped in October 2003, at about 50% of the planned accrual, when the NCIC MA.17 trial showed that letrozole therapy significantly improved disease-free survival after the completion of 5 years of tamoxifen treatment. The treatment was unblinded at that time and patients randomized to placebo were offered exemestane.

After unblinding, 560 of the 783 patients receiving exemestane continued on exemestane while 344 of 779 patients initially receiving placebo switched to exemestane.

After a median follow-up of 30 months, despite the crossover, a borderline statistically significant, the results showed a 32% improvement in disease-free survival in favor of exemestane (91% vs 89%, P = .07). Distant disease-free survival was not significantly different with exemestane versus placebo (94% vs 93%, P = .13).

The subset of patients with tumors larger than 2 cm (P = .04) or node-positive disease (P = .01), and those who received prior adjuvant chemotherapy (P = .05) showed a significant difference in disease-free survival with exemestane compared with placebo, according to Dr. Mamounas.

No difference in overall survival was observed; 13 deaths occurred in the placebo group and 16 in the exemestane arm, (98% vs 95%, relative risk = 1.2, P = .63).

Toxicity was assessed until the study was unblinded. Among patients in both groups, 1% developed grade 4 toxicity, while 9% and 6% developed grade 3 toxicity with exemestane and placebo, respectively (P = .03). The most common grade 3/4 toxicities were arthralgia (1.0% vs 0.5%), fatigue (0.9% vs 0.5%), and bone pain (0.5% vs 0.7%) in the exemestane and placebo groups, respectively.

Six months after the study was unblinded, 28 fractures occurred in the exemestane arm and 20 in placebo arm (P = .33). No differences were experienced in quality of life categories: vasomotor, psychosocial, physical, or sexual symptoms.

"The reductions in disease-free, relapse-free, and distant disease-free survival were of similar magnitude to those seen in the NCIC MA.17 with letrozole and in the ABCSG 6 trial with anastrozole," Dr. Mamounas said.

"Results from the IES show a clear benefit for women who receive [exemestane] after 2 to 3 years of tamoxifen. The B-33 study results presented today show that [exemestane] is also effective in the extended adjuvant setting after 5 years of tamoxifen," stated Professor Charles Coombes, lead investigator for the landmark Intergroup Exemestane Study (IES) and director of cancer medicine, Imperial College, London, United Kingdom, in a written release.


[Presentation title: Benefit From Exemestane (EXE) as Extended Adjuvant Therapy After 5 Years of Tamoxifen (TAM): Intent-to-Treat Analysis of NSABP B-33. Abstract 49]

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