Letrozole, a new oral aromatase inhibitor: Randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer

Background: The study compares letrozole and aminoglutethimide (AG), astandard therapy for postmenopausal women with advanced breast cancer,previously treated with anti-oestrogens.Patients and methods: 555 women were randomly assigned letrozole 2.5 mgonce daily (n = 185), letrozole 0.5 mg once daily (n = 192) oraminoglutethimide 250 mg twice daily with corticosteroid support (n = 178)in an open-label, multicentre trial. The primary endpoint was objectiveresponse rate (ORR), with time events as secondary. ORR was analysed ninemonths after enrolment of the last patient, while survival was analysed 15months after the last patient was enrolled. We report the results of theseanalyses plus an extended period of observation (covering a total durationof approximately 45 months) to determine the duration of response andclinical benefit.Results: Overall objective response rates (complete + partial) of19.5%, 16.7% and 12.4% were seen for letrozole 2.5 mg,0.5 mg and AG respectively. Median duration of response and stable diseasewas longest for letrozole 2.5 mg (21 months) compared with letrozole 0.5 mg(18 months) and AG (14 months). Letrozole 2.5 mg was superior to AG in timeto progression, time to treatment failure and overall survival.Treatment-related adverse events occurred in fewer patients on letrozole(33%) than on AG (46%). Transient nausea was the most frequentevent with letrozole (7% on 0.5 mg, 10% on 2.5 mg, 10%on AG), rash with AG (11%, 1% on 0.5 mg, 3% on 2.5 mgletrozole).Conclusions: Letrozole 2.5 mg offers longer disease control thanaminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausalwomen with advanced breast cancer, previously treated with anti-oestrogens.