In Austria, about 24% of women with initially diagnosed breast cancer (BC) have locally advanced and about 5% have metastatic disease, corresponding to a 5-year relative survival of 60% and 10%, respectively.
Everolimus is a selective inhibitor of mTOR (mammalian target of rapamycin) and thus reduces cell proliferation, angiogenesis and glucose uptake. Everolimus was licensed in the U.S. and the EU for the new indication "treatment of postmenopausal women with advanced HR-positive, HER2-negative breast cancer in combination with exemestane, after failure of treatment with a non-steroidal aromatase inhibitor" in July 2012. This approval was based on the interim results of a phase III trial (BOLERO-2) showing an increased progression-free survival of about 4 months for everolimus in combination with exemestane compared to exemestane alone. Overall tumour response, almost all of them being partial responses, was significantly higher in favour of the everolimus-exemestane group (12.6% vs. 1.7%). Although fewer deaths occurred in the intervention group, the analysis of overall survival showed no advantage, but those data were premature.
Results on the quality of life differed depending on the time of analysis. More patients in the everolimus-exemestane group had adverse events, serious adverse events, and events that led to a discontinuation of the whole study treatment.
Final data allowing firm conclusions can be expected in 2015. These as well as the results of an upcoming 3-arm phase III trial comparing everolimus alone or in combination with exemestane versus capecitabine alone (BOLERO-6) will be helpful in deciding on the use of everolimus in the therapy of locally advanced or metastatic BC.