VIENNA--The fourth-generation aromatase inhibitor letrozole(Drug information on letrozole) has become the first drug of its class to outperform megestrol(Drug information on megestrol) acetate as a second-line hormonal therapy for postmenopausal women with metastatic breast cancer who relapsed or progressed during tamoxifen(Drug information on tamoxifen) (Nolvadex) therapy.
Speaking at the 21st Congress of the European Society for Medical Oncology (ESMO), Geoffrey Falkson, MD, of the University of Pretoria, reported the results of a double-blind randomized trial that enrolled 551 patients from 10 countries around the world.
Letrozole yielded a higher response rate, more long-lasting responses, and a longer time to treatment failure than the progestin, Dr. Falkson said, and was better tolerated, produced fewer side effects, and caused much less weight gain.
The objective response rate among women receiving the optimal 2.5 mg/day letrozole dose was 24%, significantly better than the 16% response rate seen in the progestin group, Dr. Falkson reported.
The median duration of response has not yet been reached in the letrozole group but was 18 months with megestrol. Particularly important, he said, is the time to treatment failure: 5.1 months with letrozole vs 3.9 months with megestrol.
Median survival duration was 731 days with letrozole and 660 days with meges-trol, although this difference fell short of reaching statistical significance.
The rate of adverse cardiovascular events, chiefly thromboembolism, was 1.7% among letrozole-treated patients vs 10.1% in the megestrol group.
Among women taking letrozole, 18% gained more than 5% of their body weight vs 30% of those on megestrol; 6% on letrozole gained more than 10% of body weight vs 12% on megestrol.
Letrozole was associated with less fatigue and dyspnea, and with less deterioration in performance status. The lesser side effect burden of letrozole translated into a discontinuation rate of only 3.4% vs 10% for megestrol.