In women with HER2-positive advanced or metastatic breast cancer, treatment with trastuzumab is associated with prolonged survival but also increases the risk of developing heart problems, a new systematic review shows. However, the review, published inThe Cochrane Library, concludes that more women benefit from use of trastuzumab than are harmed.
The review focuses on treatment for women with advanced stage breast cancer who have tested HER2-positive. About 1 in 5 women with breast cancer are HER2-positive. The prognosis for HER2-positive patients is usually worse because the high levels of HER2 on their tumour cells make their cancer more aggressive.
The monoclonal antibody trastuzumab is designed to target these specific types of tumours. It has been recommended for treating women who have HER2-positive advanced breast cancer since 1998 in the USA and 2000 in the EU.
The authors reviewed data from seven trials involving a total of 1,497 HER2-positive women with metastatic breast cancer. The women were given trastuzumab in combination with other drugs, either as a first-line treatment or later therapy, when their cancer had progressed.
Overall survival rates two years after starting the trials were higher for women who were given trastuzumab than for those on regimens that did not include the drug. Women on trastuzumab also gained another two to eleven months without further progression of their cancers. The drug was most effective when it was used as a first-line treatment or in combination with taxanes.
This review suggests that, for women with advanced breast cancer, trastuzumab has been linked to significant life expectancy gains. In particular, the authors found that “trastuzumab improved overall survival and progression-free survival in HER2-positive women with metastatic breast cancer, but it also increased the risk of cardiac toxicities, such as congestive heart failure and LVEF decline. The available subgroup analyses are limited by the small number of studies. Studies that administered trastuzumab as first-line treatment, or along with a taxane-based regimen, improved mortality outcomes. The evidence to support the use of trastuzumab beyond progression is limited. The recruitment in three out of seven studies was stopped early and in three trials more than 50% of patients in the control groups were permitted to switch to the trastuzumab arms at progression, making it more difficult to understand the real net benefit of trastuzumab. Trastuzumab is generally used for women with HER2-positive early breast cancer in clinical practice, while women enrolled in most of the trials in the metastatic setting were naive to trastuzumab. The effectiveness of trastuzumab for women relapsing after adjuvant trastuzumab is therefore still an open issue, although it is likely that the majority are being offered it again.”
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Balduzzi S, Mantarro S, Guarneri V,et al.Trastuzumab-containing regimens for metastatic breast cancer. Cochrane Database Szst Rev 2014; June 12. 6:CD006242. [Epub ahead of print]