The FDA ( U.S. Food and Drug Administration ) approved Aromasin ( Exemestane tablets ) for adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer following two-to-three years of Tamoxifen for a completion of five consecutive years of adjuvant hormonal therapy.
The approval was based on the Intergroup Exemestane Study ( IES ) which showed that patients who switched to Aromasin after two-to-three years of Tamoxifen, for a combined total of five years of therapy, had 31 percent more protection from cancer recurrence than those who remained on five years of tamoxifen therapy.
This landmark study, published in the New England Journal of Medicine ( NEJM ), established the superiority of switching to Aromasin rather than remaining on Tamoxifen.
Following its publication, the American Society of Clinical Oncologists and the National Comprehensive Cancer Network updated their guidelines to support the use of a new switch regimen using Aromasin adjuvant treatment.
The IES trial involved over 4,700 postmenopausal women with estrogen-receptor positive breast cancer who were followed for an average of 35 months.
Patients receiving Aromasin experienced a significant reduction in the risk for recurrence of the disease, compared to those continuing on Tamoxifen.
This reduction includes fewer local and distant tumors as well as new cancers in the other breast.
Important safety information
Aromasin tolerability in postmenopausal women with early breast cancer was evaluated in two well-controlled trials: the IES study and the 027 study ( a randomized, placebo-controlled, double-blind, parallel group study specifically designed to assess the effects of Exemestane on bone metabolism, hormones, lipids and coagulation factors over 2 years of treatment ).
The median duration of adjuvant treatment was 27.4 months and 27.3 months for patients receiving Exemestane or Tamoxifen, respectively, within the IES study and 23.9 months for patients receiving Exemestane or placebo within the 027 study.
Median duration of observation after randomization for Exemestane was 34.5 months and for Tamoxifen was 34.6 months.
Median duration of observation was 30 months for both groups in the 027 study.
Aromasin was generally well tolerated and adverse events were usually mild to moderate.
Within the IES study discontinuations due to adverse events occurred in 6.3% and 5.1% of patients receiving Aromasin and Tamoxifen, respectively, and in 12.3% and 4.1% of patients receiving Exemestane or placebo within study 027.
Deaths due to any cause were 16 reported for 1.3% of the Exemestane-treated patients and 1.4% of the Tamoxifen-treated patients within the IES study.
There were 6 deaths due to stroke on the Exemestane arm compared to 2 on Tamoxifen. There were 5 deaths due to cardiac failure on the Exemestane arm compared to 2 on Tamoxifen.
The incidence of cardiac ischemic events ( myocardial infarction, angina and myocardial Ischemia ) was 1.6% in Exemestane treated patients and 0.6% in Tamoxifen treated patients in the IES study.
Cardiac failure was observed in 0.4% of Exemestane treated patients and 0.3% of Tamoxifen treated patients.
In the IES study, as compared to Tamoxifen, Aromasin was associated with a higher incidence of events in the musculoskeletal disorders and in the nervous system disorders, including the following events occurring with frequency lower than 5% ( osteoporosis [ 4.6% vs. 2.8% ], osteochondrosis and trigger finger [ 0.3% vs 0 for both events ], paresthesia [ 2.6% vs. 0.9% ], carpal tunnel syndrome [ 2.4% vs. 0.2% ], and neuropathy [ 0.6% vs. 0.1% ].
Diarrhea was also more frequent in the Exemestane group ( 4.2% vs. 2.2% ).
Clinical fractures were reported in 94 patients receiving Exemestane ( 4.2% ) and 71 patients receiving Tamoxifen ( 3.1% ).
Tamoxifen was associated with a higher incidence of muscle cramps [ 3.1% vs. 1.5% ], thromboembolism [ 2.0% vs. 0.9% ], endometrial hyperplasia [ 1.7% vs. 0.6% ], and uterine polyps [ 2.4% vs. 0.4% ].
Source: Pfizer, 2005