Abstract YR01: New treatment options in metastatic breast cancer
Authors: Johnston SRD 
Published: August 2014

Abstract
During 2013 there have been significant new data from various clinical trials of systemic therapies for metastatic breast cancer (MBC) – the issue is to what extent has this changed clinical practice. The most significant results continue to be in HER2+ MBC where novel HER2 targeted drugs given either alone or in combination with trastuzumab have re-defined the optimal treatment strategy. It would appear that dual combination therapy is superior to trastuzumab alone. In the CLEOPATRA trial the combination of the two monoclonal antibodies pertuzumab & trastuzmab with docetaxel showed a very significant improvement in progression-free survival (18.5 vs 12.4 months) compared with trastuzumab-docetaxel therapy, and in 2013 this became a new standard of care in the first-line setting. Following the results of the EMILIA trial which showed a substantial improvement in PFS (9.6 vs 6.4 months) for the antibody conjugate T-DM1 compared with lapatinib and capecitabine in the second-line setting, in the USA this option has become an approved second-line therapy. In addition, compelling data were published this year showing superiority of T-DM1 compared with docetaxel-tratsuzumab in the first-line setting. The role of lapatinib remains more uncertain, although the combination with trastuzumab recently received approval in hormone receptor negative HER2+ MBC previously treated with trastuzmab and chemotherapy. In ER+ breast cancer attempts are continuing to prevent or reverse endocrine resistance. It is clear that different endocrine therapies, including the combination of fulvestrant and anastrozole provide only 3-4 months benefit following progression on a non-steroidal aromatase inhibitor as shown in the SoFEA trial. This is in contrast to the very positive data reported for the mTOR inhibitor everolimus combined either with exemestane (BOLERO-2) or tamoxifen (TAMRAD), an approach that has become a new standard of care for endocrine resistant breast cancer. Whether benefit exists in the untreated 1st line setting for this approach remains unclear, as demonstrated by negative results from the HORIZON study. Attempts to see whether biomarkers of the PI3-kinase pathway might predict those who benefit from mTOR inhibition were presented at ASCO 2013, but failed to identify any single predictive profile. For other signalling therapies in ER+ MBC, positive results were published this year for the combination of the HDAC inhibitor entinostat with exemestane, while negative results were reported for the combination of the IGF-1R mAb therapy ganitumab with endocrine therapy. While progress with systemic therapies has been rapid with novel therapeutics in both ER+ and HER2+ breast cancer, for other subtypes (ie. triple negative MBC) no new therapeutics have emerged during the last 12 months. Instead, prospective studies (SAFIR0l) are providing personalised targeted treatment options based on molecular characterisation of key mutations / amplifications in metastatic biopsy samples, in the hope that this will ultimately provide a more efficient clinical development pathway for novel therapeutics in MBC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr YR01.