The aromatase inhibitors exemestane and anastrozole are associated with similar survival rates when used as adjuvant therapy in postmenopausal women with hormone-receptor-positive breast cancer, according to the final results of the National Cancer Institute of Canada Clinical Trials Group MA-27 trial reported at the CTRC-AACR San Antonio Breast Cancer Symposium.
After a median follow-up period of 4.1 years, the event-free survival rate—the primary endpoint—was 90.8% in the exemestane arm and 90.9% in the anastrozole arm.
There was also no difference in secondary endpoints of distant disease-free survival, disease-specific survival, and overall survival rates between the two groups, reported Paul E. Goss, MD, PhD, Director of Breast Cancer Research at Massachusetts General Hospital Cancer Center and Professor of Medicine at Harvard Medical School.
“The survival curves were super-imposable…and the event rates were similar in both arms,” he said.
Referring to the fact that exemestane is not approved for five years of upfront adjuvant endocrine therapy, while anastrozole and letrozole are, he told OT, “Sometimes the third pony is only the third pony. It may have started the race later, but not because it is slow. Exemestane is the third pony, and it's just as good as the others.”
Exemestane and anastrozole act differently, Dr. Goss explained: Anastrozole is a nonsteroidal aromatase inhibitor that profoundly and specifically suppresses circulating and intra- and peri-tumoral estrogens.
In contrast, exemestane is a potent steroidal, irreversible suicide aromatase inhibitor. “It may suppress estrogens more than anastrozole. And it has a potent pro-androgenic effect and therefore may exert a secondary antitumor effect.
“We also hypothesized that the androgenic and anabolic effects of exemestane would protect against hypercholesterolemia and counteract bone loss, both of which are associated with the other aromatase inhibitors, which is just what happened,” he said.
PAUL E. GOSS, MD, PH...Image Tools
The MA-27 trial, which was funded by Pfizer, which makes exemestane (Aromasin), enrolled 7,576 postmenopausal women with localized hormone-receptor-positive invasive breast cancer.
Their median age was 64 years, and about 95% were white, 69% had undergone lumpectomy, 31% had received adjuvant chemotherapy, and 4% had received trastuzumab.
The women were randomized to receive anastrozole (1 mg/day) or exemestane (25 mg/day).
The hypothesis at the start of the trial was that use of exemestane would improve the event-free survival rate to 89.9% vs 87.5% for anastrozole.
However, the drugs turned out to have similar clinical outcomes, Dr. Goss reported.
The overall survival rate was about 94% in both groups, the distant disease-free survival rate was about 96%, and the disease-specific survival rate was about 97% in both arms.
Subgroup analyses showed that the event-free survival rate was similar in the two arms regardless of nodal status at baseline or use of adjuvant chemotherapy.
Different Safety Profiles
When it comes to adverse events, however, the drugs have different safety profiles.
Acne, elevated liver enzyme levels, and masculinization, although rare, were significantly more common in the exemestane arm. On the other hand, exemestane was associated with less vaginal bleeding (1% vs 2%), hypertriglyceridemia (2% vs 3%), hypercholesterolemia (15% vs 18%), and self-reported osteoporosis (31% vs 35%) than anastrozole was. The fracture rates were similar for both drugs.
Treatment adherence was a problem in both groups, with 30% to 40% of the patients discontinuing their study drug.
Cost an Issue
During the question-and-answer session, Steven E. Vogl, MD, a clinician from the Bronx, NY, called cost “the elephant in the room”—In New York, anastrozole is available generically for around $16 a month, while exemestane is still on patent and costs around $400, he said. “It's a no brainer.”
Dr. Goss replied that the different aromatase inhibitors are coming off patent at different times in different parts of the world. “Exemestane will be off patent on the near future,” making cost less of an issue.
The bottom line, he said, is that “exemestane is comparable to anastrozole and provides a new option for five years of upfront adjuvant therapy for patients with hormone receptor-positive early breast cancer.”
© 2011 Lippincott Williams & Wilkins, Inc.