Arimidex Update

Data was presented last week at the San Antonio, Breast Cancer Conference in Texas (SABCS) from a meta-analysis of three early breast cancer trials where tamoxifen was replaced with an anastrozole (Arimidex) after two to three years of tamoxifen.

Key international trials including over 4000 women were collated and presented by Dr. Jonat at a median follow-up of 30 months. The results of the studies revealed proportional benefits of 29% in overall survival, 45% in event-free survival and 39% in distant recurrence-free survival for women switched to anastrozole after 2-3 years of tamoxifen. Absolute benefits were real but small in these good prognosis women.

Slide One shows that the absolute risk of all recurrence events was 8.0% (n = 159) for patients taking tamoxifen and 4.6% (92) for patients who were switched to anastrozole.

Slide Two shows a highly significant improvement in disease-free survival for patients taking anastrozole.

Slide Three shows that 90 patients died (4.5%) in the tamoxifen arms of the trials, compared to 66 patients (3.3%) who were switched to anastrozole.

Slide Four shows a small but statistically significant (p=0.038) improvement in overall survival associated with switching to anastrozole compared to continuing with tamoxifen .

Slide Five is a Forest plot showing a significant improvement in all parameters.

What does all this mean?

Three different types of studies have now shown aromatase inhibitors to be slightly better than tamoxifen at preventing breast cancer recurrence, at least in the first few years of follow-up. The studies were of three types:

1: Comparing adjuvant aromatase inhibitors for five years to adjuvant tamoxifen for five years (e.g. ATAC trial of anastrozole, BIG-98 trial of letrozole)

2: Giving two to three years of tamoxifen followed by a switch to an aromatase inhibitors (e.g. this meta-analysis)

3: Taking five years of tamoxifen and then being randomised to adjuvant aromatase inhibitors or placebo (e.g., MA 17 study using letrozole)

We have previously reviewed the incidence of side effects of anastrozole versus Tamoxifen (See http://www.bci.org.au/public/news/media/1104%5F7media.htm)

The main adverse effects relate to arthralgia (36% anastrozole vs 29% Tamoxifen) and the incidence of osteoporosis. Fractures were seen in 11% in the anastrozole group and 8% in Tamoxifen group, although hip fractures only occurred in 1.2% v 1.0%. Conversely, the rare but real incidence of venous thrombosis and endometrial cancer known to be associated with tamoxifen does not apply to aromatase inhibitors.

At the recent Westmead BCI public forum, Dr. Nicholas Wilcken, Research Director of BCI, stated that “once size doesn’t fit all”. For patients who have good prognosis disease and tumours that are strongly ER positive, tamoxifen may still be the best option particularly if there is a family or personal history of osteoporosis.

“For patients with more extensive disease, e.g. with positive-nodes or larger tumours, it may be better to go straight to an aromatase inhibitor,” Dr. Wilcken said.

For patients who are half way through their tamoxifen, if they are tolerating this well and their disease risk is low it may be better to continue with the tamoxifen. If they are having sufficient hot flushes or problems with vaginal discharge then an aromatase inhibitor may be a reasonable switch. A recent report did show a slight increase in sexual morbidity including vaginal dryness and reduced libido with aromatase inhibitors. This should also be taken into account when discussing this choice with patients.

The trials have shown a slight excess of cardiac events and slightly fewer strokes in the aromatase inhibitor arms, but it is not yet clear if these are real effects. Whether there are any long term side effects (e.g. 10 – 20 years) for aromatase inhibitors is not known.

For patients who have completed five years of tamoxifen the Adjuvant! calculator. www.adjuvantonline.com calculates the additional benefit of five years of letrozole after five years of tamoxifen (based on the MA 17 data). Once again, patients who benefit most from letrozole after 5 years of tamoxifen are those who were at high risk of recurrence at diagnosis (i.e. five years earlier), such as patients with larger tumours or node-positive disease. The absolute benefit for patients who are node-negative with small tumours is usually less than 1%. The benefit may not be worth the risk.

New guidelines are being developed by the National Breast Cancer Centre regarding adjuvant aromatase inhibitors and from 1st December 2005, the government has funded adjuvant Arimidex (anastrozole) under the PBS scheme.

Last Updated on Tuesday, 09 February 2010 12:14