In this phase II clinical study, 122 patients were randomized to either exemestane (25 mg/day) or tamoxifen (20 mg/day). The results indicate that exemestane was well-tolerated. Women treated with exemestane experienced the following grade 2/3 side-effects compared with those treated with tamoxifen: dyspnea (10 % vs. 8 %), edema or swelling (2 % vs. 11 %), grade 2/3 fatigue (13 % vs. 13 %), hot flashes (3 % vs. 14 %) and bone pain (10 % vs. 15 %). No patients were withdrawn from treatment due to toxicity. Moreover, patients treated with exemestane had three times the response rate (complete plus partial responses) in shrinking tumors (41 % vs. 17 %) relative to tamoxifen-treated patients.
"Although a formal statistical comparison between the two study arms is not allowed in the setting of this phase II clinical trial, the results were found very promising," said Robert J. Paridaens, M.D., Ph.D., professor and head of the medical oncology clinic, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium, and lead investigator for the EORTC Breast Group. "The results lead to the European Organization for Research and Treatment of Cancer (EORTC), the organization that conducted the clinical trial, decision to extend the study in a phase III trial, for which the accrual of 342 patients was recently completed. The final results with statistical comparison of efficacy of both arms (exemestane versus tamoxifen) will be available by end of this year."
Exemestane currently is indicated for the treatment of advanced breast cancer in postmenopausal women whose tumors have stopped responding to tamoxifen. It is the first and only oral drug in a class of aromatase inactivators. Its unique mechanism of action works by selectively targeting and irreversibly binding to the aromatase enzyme. This enzyme is required to produce estrogen in the breast. Since some breast cancer cells need estrogen to survive, once exemestane binds to an enzyme, the enzyme cannot produce estrogen again.
This mechanistic feature, coupled with other clinical trial results to date, prompted the EORTC to conduct this Phase II study. Based on the results, the EORTC has expanded the trial into a Phase III trial of identical design. The efficacy of exemestane in the adjuvant treatment of breast cancer is being examined in worldwide clinical trials involving more than 7,000 patients. In addition, its potential in the prevention of breast cancer is under evaluation.
Exemestane is marketed by Pfizer under the brand name AROMASIN® (exemestane tablets).
About the EORTC
The European Organization for Research and Treatment of Cancer (EORTC), created in 1962, is an international research organization registered under Belgian law. It promotes, conducts and coordinates multi-disciplinary cancer research in 32 countries and represents a unique network of more than 2,500 scientists and clinical investigators organized in 30 groups and 4 task forces, in about 300 cancer centers and clinics. The ultimate goal of the EORTC is to improve the standard of cancer treatment in Europe, through the development of new drugs and other innovative approaches, and to test effective therapeutic strategies, using drugs, which are already commercially available, or surgery and radiotherapy. In this way, the EORTC facilitates the passage of experimental discoveries into state-of-the-art treatment. Such international cooperation between major European centers minimizes the delay between the discovery of new anti-cancer agents and their therapeutic benefit for patients with cancer.
For more information about the EORTC's research activities, please have a look at our website: http://www.eortc.be
Journal
Annals of Oncology