Exemestane (Aromasin) was no better than anastrozole (Arimidex) at reducing cancer recurrence in postmenopausal women with hormone receptor-positive primary breast cancer, according to final data from the NCIC CTG MA.27 trial presented at the San Antonio Breast Cancer Symposium. MA.27 is the first definitive early breast cancer trial comparing a nonsteroidal and a steroidal aromatase inhibitor as adjuvant therapy. Anastrozole, the nonsteroidal aromatase inhibitor, is approved as single-agent adjuvant therapy; exemestane, the steroidal aromatase inhibitor, is approved as sequential therapy in women who have received 2 to 3 years of tamoxifen.
"MA.27 tested the hypothesis that exemestane would have greater efficacy and better end-organ safety than anastrozole for several reasons," said principal investigator Paul E. Goss, MD, Massachusetts General Hospital, Boston. He noted that exemestane is an irreversible and more potent aromatase inhibitor than anastrozole and does not induce intratumoral aromatase. "Through its mild androgenic activity, [exemestane] may exert a second anti-tumor effect and [produce] a more favorable bone and lipid metabolism profile than anastrozole."
The investigators for MA.27 randomized 7576 women with breast cancer to treatment for 5 years with 1 mg of anastrozole or 25 mg of exemestane daily. Initially, the study also tested the role of the cyclooxygenase (COX)-2 inhibitor celecoxib (Celebrex) in combination with an aromatase inhibitor, but Goss said they discontinued this arm early on during the trial after other studies and clinical evidence associated COX-2 inhibitors with cardiovascular toxicity.
"Exemestane was not superior to anastrozole, which was the primary objective of the trial," said Goss. "There were no significant differences in any outcome variables. The event-free survival curves were superimposable at 4.1 years of follow-up," he added.
The disease-free survival rate was 91% in both arms of the study. Events--recurrence, new breast cancer, and deaths--were observed in 9.2% of patients taking exemestane versus 9.1% of patients randomized to anastrozole (P
= .85). Nearly 4% of patients in each arm developed distant recurrence. By 3 years, approximately one-fourth of patients in each arm had discontinued treatment.
In subset analyses, the curves were again superimposable, with nonsignificant P values, said Goss. This was also true for a comparison between women who had prior adjuvant chemotherapy and women who did not. Rather than viewing the trial as a failure for not demonstrating superiority for one regimen or another, Goss said, "We see this as providing a new option for 5 years of upfront adjuvant therapy."
Both arms had similar rates of menopauselike symptoms, although vaginal bleeding was less frequent in women taking exemestane. Cardiovascular events were infrequent and occurred at similar rates and with similar intensity in both arms. Hypertriglyceridemia and hypercholesterolemia were less likely to occur in patients receiving exemestane, and patients taking exemestane were less likely to report a new diagnosis of osteoporosis. Clinical fracture rates were similar in both study arms, however.
"In keeping with its steroidal structure, exemestane may cause mild androgenic effects and lower rates of osteoporosis,"Goss said. "Event rates were low in both arms. At 4 years, 91% of women were diseasefree, probably reflecting the low-risk population and improvements in breast cancer care," he said. "Endorgan effects were slightly different between the drugs, and that may be clinically important."
"The aromatase inhibitors are coming off patent soon, and generic versions are appearing around the world. We believe this result provides patients with additional choices, depending on local access to care and cost," said Goss. "Because the side effect profiles are somewhat different, if patients have symptoms on one drug they can try another one without doing harm," he added. Exemestane is not currently approved in the United States as initial adjuvant treatment in this patient population. Abstract S1-1
___________________________________________________________________Goss PE, Ingle JN, Chapman, J-AW, et al. Final analysis of NCIC CTG MA.27: A randomized phase III trial of exemestane versus anastrozole in postmenopausal women with hormone receptor positive primary breast cancer. Paper presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12, 2010; San Antonio, TX.