Femara - Letrozole geeft beter effect op zietkevrije tijd en overall overleving dan Tamoxifen.

9 april zie ook informatie over de mammaprint, een genen test specifiek voor borstkanker

d.d. juni 2003:

Letrazole, een aromaseremmer is superieur aan Tamoxifen in effect bij hormoongevoelige borstkanker aldus een gerandomiseerde fase III studie gepubliceerd in The Journal of Clinical Oncology June 1 2003: 2101-2109.

In een gerandomiseerde studie in een aantal Europese ziekenhuizen onder 939 vrouwen (post-menopausaal) met hormoonbepaalde borstkanker, al of niet met uitzaaiïngen is letrazole een zogeheten aromaseremmer vergeleken met Tamoxifen. Het aanslaan van de behandeling was bij letrazole aanmerkelijk hoger - (32% vs 21%), en ook de tijd tussen een recidief na behandeling was significant langer - (9.4 vs 6.0 maanden) - bij het gebruik van letrazole hoewel de overlevingstijd niet significant hoger was (34 vs 30 maanden). Wel een beetje verschil dus , maar te weinig om als significant te kunnen worden benoemd. De reden die de onderzoekers daarvoor geven is dat de vrouwen tijdens de studie over mochten stappen van de ene behandeling naar de andere als zij dat wilden. Veel vrouwen zijn halverwege blijkbaar overgestapt op letrazole wanneer de tamoxifen niet aansloeg of andersom en volgens de onderzoekers zou dat een effect kunnen hebben gehad op de uiteindelijke overlevingstijd. Want ook dat wordt benadrukt: de overlevingstijd van hormoonbepaalde borstkanker wordt ook met letrazole slechts met enkele maanden verlengd. Hieronder een officieel persbericht over deze studie van de producent van letrazole: http://www.veritasmedicine.com

Letrazole is Superior to Tamoxifen as First Line Therapy of Advanced Breast Cancer in Post-menopausal Women
06/13/2003

The majority of breast cancers in post-menopausal women express the estrogen receptor (ER) and are sensitive to hormonal therapy. The drug tamoxifen, which prevents the hormone estrogen from binding to ER, has been the gold standard hormonal agent in breast cancer treatment. It has an established role both as part of the adjuvant treatment of early stage breast cancers, and as a first line agent in the treatment of advanced (metastatic) breast cancer. There has been much recent interest in another class of hormonal agents, the aromatase inhibitors. These drugs work by inhibiting the body’s ability to make estrogen, and have been shown to have efficacy in advanced breast cancer that has failed prior treatment with tamoxifen. Some early trials have suggested that aromatase inhibitors may be at least as effective as tamoxifen in the treatment of post-menopausal women with advanced ER-positive breast cancer. Now an update of one of these randomized trials has demonstrated that letrazole, a third generation aromatase inhibitor, is superior to tamoxifen when used as the first line treatment of post-menopausal women with ER-positive advanced breast cancer.

In this study, performed at multiple centers in Europe and Asia, 939 post-menopausal women with advanced (metastatic) breast cancer whose hormone receptor status was either positive or unknown were enrolled. They were randomized to receive either tamoxifen alone or letrozole alone and followed for a median of 32 months. Of note, if the patients’ tumor progressed on treatment, they were allowed to switch to the other drug. The women receiving letrozole had a higher overall response rate (32% vs 21%), and longer time to tumor progression (9.4 vs 6.0 months) than those receiving tamoxifen. Overall survival was slightly higher in the letrazole group (34 vs 30 months) but was not statistically significant. Total time of endocrine therapy (ie how long before the women required standard chemotherapy) was also significantly longer for the women receiving letrazole (16 vs 9 months). These data show that letrazole is superior to tamoxifen in these women.

This is the first large study to clearly demonstrate that a third-generation aromatase inhibitor is superior to standard tamoxifen therapy in the treatment of advanced breast cancer in post-menopausal women and may well change clinical practice. However one has to note that there was no change in overall survival seen between tamoxifen and letrazole. The authors of the study suggest that this may be due to the fact that there was a large amount of cross over. That is, many women in this trial whose tumor progressed on tamoxifen were allowed to switch to treatment with letrazole. This cross over treatment effect may have minimized any effect on overall survival. Aromatase inhibitors are not for everyone though. These agents may be less effective in pre-menopausal women whose ovaries are quite active in producing estrogen. In these women tamoxifen remains the standard first line hormonal agent in ER (+) breast cancer. Another major question is whether these promising results will also carryover into the treatment of earlier stage breast cancer. Randomized trials comparing tamoxifen vs aromatase inhibitors in the adjuvant treatment of early stage ER(+) breast cancers are currently ongoing. Results from these trials may further expand the evolving role of aromatase inhibitors in the hormonal treatment of breast cancer.

Reference:

Phase III Study of Letrozole Versus Tamoxifen as First-Line Therapy of Advanced Breast Cancer in Postmenopausal Women: Analysis of Survival and Update of Efficacy From the International Letrozole Breast Cancer Group

Henning Mouridsen, Mikhail Gershanovich, Yan Sun, Ramón Pérez-Carrión, Corrado Boni, Alain Monnier, Justus Apffelstaedt, Robert Smith, Harm P. Sleeboom, Fritz Jaenicke, Anna Pluzanska, Magdolna Dank, Dominique Becquart, Poonamalle P. Bapsy, Eeva Salminen, Ray Snyder, Hilary Chaudri-Ross, Raquel Lang, Peter Wyld, and Ajay Bhatnagar

Journal of Clinical Oncology Jun 1 2003: 2101-2109.