A large double-blinded randomized trial (EORTC-10967 [ICCG-96OEXE031-C1396-BIG9702]) of 4,742 patients compared continuing tamoxifen with switching to exemestane for a total of 5 years of therapy in women who had received 2 to 3 years of tamoxifen.[156,157] After the second planned interim analysis, when median follow-up for patients on the study was 30.6 months, the results were released because of a highly significant (P < .005) difference in DFS (HR, 0.68) favoring the exemestane arm.[Level of evidence: 1iDii] After a median follow-up of 55.7 months, the HR for DFS was 0.76 (95% CI, 0.66–0.88; P = .001) in favor of exemestane. At 2.5 years after randomization, 3.3% fewer patients on exemestane had developed a DFS event (95% CI, 1.6–4.9). The HR for OS was 0.85 (95% CI, 0.7–1.02; P = .08).[Level of evidence: 1iA] Women on exemestane had significantly more arthralgia, diarrhea, hypertension, fractures, arthritis, musculoskeletal pain, carpal tunnel syndrome, insomnia, and osteoporosis, but women on tamoxifen had significantly more gynecologic symptoms, muscle cramps, vaginal bleeding and discharge, thromboembolic disease, endometrial hyperplasia, and uterine polyps. (Refer to the PDQ summary on Gastrointestinal Complications for information on diarrhea and for information on insomnia, refer to the PDQ summary on Sleep Disorders.)
A large, randomized trial of 9,779 patients compared DFS of postmenopausal women with hormone receptor–positive breast cancer between initial treatment with sequential tamoxifen for 2.5 to 3 years followed by exemestane for a total of 5 years versus exemestane alone for 5 years. The primary endpoints were DFS at 2.75 years and 5.0 years. Five-year DFS was 85% in the sequential group and 86% in the exemestane-alone group (HR, 0.97; 95% CI, 0.88–1.08; P = .60).[Level of evidence: 1iDii] The results of this trial support the use of exemestane, either sequentially after tamoxifen or as initial treatment for early-stage hormone receptor–positive breast cancer in postmenopausal women.
The mild androgen activity of exemestane prompted a randomized trial to evaluate whether exemestane might be preferable to anastrozole, in terms of its efficacy and toxicity, as upfront therapy for postmenopausal women diagnosed with hormone receptor-positive breast cancer.[Level of evidence: IiiA] The NCIC CTG MA.27 (NCT00066573) trial randomly assigned 7,576 postmenopausal women to receive 5 years of anastrozole versus exemestane. At a median follow-up of 4.1 years, no difference in efficacy was seen. Some differences in toxicities between the two drugs were seen. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent for patients on exemestane, while mild liver-function abnormalities and rare episodes of atrial fibrillation were less frequent for patients on anastrozole. Vasomotor and musculoskeletal symptoms were similar with both drugs. Based on the results of this trial, no specific aromatase inhibitor is considered superior as upfront therapy for postmenopausal women with hormone receptor-positive breast cancer.