Five randomised trials were included (n=1,297): 3 phase II trials (n=191) and 2 phase IIb/III trials (n=1,106). Phase II trials are concerned with dose findings, whilst phase IIb/III trials are concerned with efficacy. Consequently, results discussed in this abstract are from the 2 phase IIb/III trials.
Objective response: overall, 19.5 and 23.6% of patients achieved an objective response with 2.5 mg/day letrozole, compared with 12.4% of patients receiving 500 mg/day aminoglutethimide (p=0.06) and 16.4% of patients receiving 160 mg/day megestrol (p=0.04). Compared to 2.5 mg/day letrozole, 0.5 mg/day letrozole was associated with poorer response rates (p=0.004). Respective complete response rates were 4.9 and 6.9% with 2.5 mg/day letrozole, 4.7 and 3.2% with 0.5 mg/day letrozole, 1.1% with aminoglutethimide and 4.2% with megestrol. The median duration of response with letrozole (2.5 mg/day) was 24 and 33 months, compared to 15 months with aminoglutethimide and 18 months with megestrol (p=0.02).
Progression or failure time: letrozole (2.5 mg/day) was significantly superior to aminoglutethimide (risk ratio, RR 0.72, 95% confidence interval, CI: 0.57, 0.92, p=0.008), but not megestrol (RR 0.8, 95% CI: 0.62, 1.02, p=0.07). A similar analysis showed letrozole (2.5 mg/day) was significantly superior to both comparators with respect to time to treatment failure: aminoglutethimide (RR 0.7, 95% CI: 0.55, 0.88, p=0.003) and megestrol (RR 0.77, 95% CI: 0.61, 0.99, p=0.04).
Overall survival: letrozole (2.5 mg/day) was associated with an increased median survival time of 8 months compared to aminoglutethimide (RR 0.64, 95% CI: 0.49, 0.85, p=0.002), and 3 months compared to megestrol (RR 0.82, 95% CI: 0.63, 1.08, p=0.15). Letrozole 2.5 mg/day was significantly superior to the 0.5 mg/day dosage with respect to overall survival (p<0.04).
Quality of life: one trial reported quality of life data, and no major differences were observed between patients receiving letrozole and megestrol.
Adverse events: the most commonly reported adverse events judged to be related to letrozole (2.5 mg/day) were headache (1.1 and 7%), nausea (10.3 and 6%), fatigue (3.2 and 5%), hot flushes (4.9 and 5%), peripheral oedema (6%), rash (2.7%), somnolence (3.2%), vomiting (3.8%), and hypercholesterolaemia (3.8%). The majority of events were reported as mild-to-moderate in severity. Serious adverse events were reported in 10% of patients receiving letrozole (2.5 mg/day) versus 29% treated with megestrol, and in 0 versus 2.8% of aminoglutethimide recipients. No dose effect with respect to tolerability was evident with letrozole up to a dosage of 2.5 mg/day for the one trial in which this was reported.