EDMONTON, CanadaIn what Jean-Marc Nabholtz, MD, calls the first trials challenging tamoxifen(Drug information on tamoxifen) as the primary drug of choice in postmenopausal women with advanced breast cancer, anastrozole(Drug information on anastrozole) (Arimidex, a nonsteroidal aromatase inhibitor) proved as effective as tamoxifen (Nolvadex). Dr. Nabholtz, of the University of Alberta, Edmonton, Canada, reported the results at the San Antonio Breast Cancer Symposium.
Trial 0030, conducted at 97 centers in the United States and Canada, included 353 postmenopausal patients with advanced breast cancers that were ER and/or PR positive (90% of patients) or hormone status unknown. Patients were randomized to receive1 mg/d of anastrozole or 20 mg/d of tamoxifen. Patients were treated until disease progression.
This trial was a follow-up to trial 0027, conducted at 83 centers in Europe and the rest of the world, which included 668 patients. The two trials were designed to allow analysis of the combined data.
A major difference in the two trials was the greater number of patients with receptor status unknown in the European trial. In the European trial, the population was far from being a pure population of patients known to be sensitive to endocrine therapy, Dr. Nabholtz said, since about 55% of the patients had unknown receptor status.
In trial 0030, the number of patients with prior adjuvant therapy was about the same (40% in both arms) as was the number who had received prior adjuvant endocrine therapy (about 20%). In terms of the extent of metastatic disease, the only difference between the two groups was in soft tissue presentation: 10.5% in the anastrozole group vs 18% in the tamoxifen group, Dr. Nabholtz said. Both groups had extensive visceral presentation: about 48%. In the European trial, fewer patients had visceral disease (about 30%).
The objective response rates in the North American trial were 21.1% for anastrozole vs 17% for tamoxifen. When adding stable disease of at least 24 weeks, which has now emerged as an important concept in the assessment of hormonal therapy benefits, Dr. Nabholtz said, a significant clinical benefit was observed in favor of anastrozole (59% vs 46% for tamoxifen) (P = .0098).
The rate of disease progression was 67% with anastrozole vs 76% with tamoxifen, and median time to progression was 11.1 months for anastrozole vs 5.6 months for tamoxifen (P = .005).
When the data from the two trials were combined, the objective response rate was 29% for anastrozole vs 27.1% for tamoxifen. Clinical benefit was 57.1% for anastrozole vs 52% for tamoxifen.
The rate of disease progression was 71% in the anastrozole patients and 76% with tamoxifen; median time to progression was 8.5 months for anastrozole and 7 months for tamoxifen.
The numerical advantage for anastrozole with respect to time to progression in the combined analysis was not significant when all patients were included (P = .103) but did prove significant when only patients known to be receptor positive were included in the analysis (P = .022).
Both drugs were well tolerated, with fewer thromboembolitic episodes in the anastrozole patients (7.6% vs 4.5%, although this was not significant) and fewer vaginal bleeding problems with anastrozole.
Dr. Nabholtzs team concluded from these two large trials that anastrozole is at least as effective as tamoxifen as first-line treatment of advanced breast cancer in postmenopausal women.
There is a suggestion of an efficacy benefit for anastrozole over tamoxifen in receptor-positive patients, he said, and these data, along with the good tolerability shown by patients on anastrozole, argue that this drug should be considered as an alternative to tamoxifen in the first-line treatment of advanced breast cancer in postmenopausal women.
Finally, Dr. Nabholtz urged that phase III clinical trials involving hormonal therapy should exclude patients with unknown hormone receptors and try to prove the concept with patients known to be sensitive to hormonal therapy.