Letrozole Superior to Progestin as Second-Line Postmenopausal Advanced Breast Cancer Therapy

February 1, 1997

VIENNA--The fourth-generation aromatase inhibitor letrozole has become the first drug of its class to outperform megestrol acetate as a second-line hormonal therapy for postmenopausal women with metastatic breast cancer who relapsed or progressed during tamoxifen (Nolvadex) therapy.

VIENNA--The fourth-generation aromatase inhibitor letrozole has becomethe first drug of its class to outperform megestrol acetate as a second-linehormonal therapy for postmenopausal women with metastatic breast cancerwho relapsed or progressed during 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 theresults of a double-blind randomized trial that enrolled 551 patients from10 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. Falksonsaid, and was better tolerated, produced fewer side effects, and causedmuch less weight gain.

The objective response rate among women receiving the optimal 2.5 mg/dayletrozole dose was 24%, significantly better than the 16% response rateseen in the progestin group, Dr. Falkson reported.

The median duration of response has not yet been reached in the letrozolegroup but was 18 months with megestrol. Particularly important, he said,is the time to treatment failure: 5.1 months with letrozole vs 3.9 monthswith megestrol.

Median survival duration was 731 days with letrozole and 660 days withmeges-trol, although this difference fell short of reaching statisticalsignificance.

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 bodyweight 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 lessdeterioration in performance status. The lesser side effect burden of letrozoletranslated into a discontinuation rate of only 3.4% vs 10% for megestrol.