Letrozole (Femara) is superior to tamoxifen for the treatment of breast cancer
in postmenopausal women, according to data from two international trials presented
at the European breast cancer conference (EBCC) in Brussels, on September 28.
The phase III randomised, controlled trials compared the efficacy of letrozole
with tamoxifen both as first-line treatment in postmenopausal women with advanced
breast cancer and as pre-operative treatment in postmenopausal women with primary
breast cancer.
In the first-line treatment trial, 907 postmenopausal women with hormone-sensitive
locally advanced or metastatic breast cancer were treated orally with either
letrozole (2.5mg daily) or tamoxifen (20mg daily). Efficacy was assessed by
measuring time to progression (TTP), tumour response rate and duration, rate
and duration of clinical benefit, time to treatment failure (TTF), overall survival
and tolerability. Overall survival rates for the two drugs will be analysed
once an extension to the trial has been completed at the end of 2001.
The median TTP was 9.4 months in the letrozole group compared with 6.0 months
in the tamoxifen group. Patients receiving letrozole showed a better objective
response rate than patients receiving tamoxifen (30 per cent compared with 20
per cent). There were no significant differences in the duration of response
or duration of clinical benefit for either drug. The median TTF for letrozole
was 9.1 months compared with 5.7 months for tamoxifen.
In the second trial, 337 postmenopausal women with hormone-sensitive large,
localised or locally advanced breast cancers not amenable to breast-conserving
surgery were included. Patients were treated orally with either letrozole (2.5mg
daily) or tamoxifen (20mg daily) for four months before surgery to reduce tumour
size. The number of clinical responses was significantly higher for letrozole
than for tamoxifen (55 per cent compared with 36 per cent) and more women underwent
breast-conserving surgery in the letrozole group (45 per cent compared with
35 per cent). In both studies, letrozole and tamoxifen were equally well tolerated;
the three most common adverse events for both drugs were hot flushes, nausea
and hair thinning.
Commenting on the trial results, Dr Stephen Johnston (consultant oncologist,
Royal Marsden hospital, and member of the trial team) told The Journal on October
2, that, until now, no studies had shown that letrozole was better than tamoxifen
but that these data did. “The benefits for patients could be enormous,”
he said. Dr Johnston added that it was important that the message to patients
was clear: “Tamoxifen is the best drug we have had and at the moment if
a tumour fails with tamoxifen then patients receive this drug [letrozole] anyway.”
A spokesman for Novartis, manufacturer of Femara, told The Journal on October
3, that an application to extend letrozole’s licensed indications to include
first-line treatment in advanced breast cancer had been submitted to the Medicines
Control Agency. He said that the company hoped to receive a positive response
before the end of this year.
Ms Kate Law (head of clinical programmes, Cancer Research Campaign) told The
Journal on October 4 that these results looked encouraging. “The meta-analyses
on tamoxifen have shown us how effective it is. If this drug can do the same,
without tamoxifen’s side effects, then this is positive news.”