IN6 ADVANCES IN CYTOTOXIC AND OTHER TARGETED THERAPY OUT OF HER2, ER AND TRIPLE NEGATIVE METASTATIC BREAST CANCERS

Abstract

transduction pathways. Particularly, in the past year, encouraging results have emerged from studies testing mammalian target of rapamycin (mTOR) inhibitors, such as the BOLERO-2 that showed an increase in the median progression-free survival from 4.1 to 10.6 months with the addition of everolimus to exemestane (central assessment), in the interim analysis (hazard ratio for progression/ death 0.36, p<0.001). Several other clinical phase II and phase III trials are underway combining anti-mTOR agents, such has BELLE-3 (BKM120 + fulvestrant), PrE0102 (fulvestrant ± everolimus) or TAMRAD (tamoxifen ± everolimus); insulin-like growth factor receptor-1 (IGFR1) inhibitors (AMG 479 + exemestane or fulvestrant); histone deacetylase (HDAC) inhibitors (vorinostat + tamoxifen) and phosphatidylinositol3-kinase/Akt (PI3K/AKT) inhibitors. So far, the most promising results come from the combination of everolimus and endocrine agents, as has been shown in the TAMRAD and BOLERO-2 studies. Because these new therapies carry a cost in terms of side effects and finances, it will be important to identify biomarkers of enhanced benefit: preliminary results in this field will be presented. Besides addressing the identification of the best partner for combination with an endocrine agent, trials examining the intermittent administration of endocrine therapy, as in prostate cancer, could also be appealing, in an attempt to obviate the menopausal symptoms experienced by patients, which are known to compromise treatment adherence, and, as a result, can “fuel” tumour resistance. Finding new targets is also sought. The androgen receptor (AR) as a target in breast cancer seems to have regained interest recently and research is underway to clarify its role both as a prognostic and predictive biomarker. The cross-talk between the AR and HER2 pathways and the relationship between AR levels and mutations in PI3K are being examined and constitute a possible new hope in the treatment of advanced breast cancer.