Abstract
ABSTRACT Introduction No specific standard treatment is currently recommended for HER2-positive advanced breast cancer (BC) patients progressing to dual HER2 blockade and to trastuzumab emtansine (TDM-1). However, several novel anti-HER2 agents are emerging and rapidly revolutionizing this setting. Among these, the FC-engineered monoclonal antibody margetuximab has recently demonstrated to slightly improve progression-free survival (PFS) compared with trastuzumab, when combined with chemotherapy for pretreated HER2-positive advanced BC. Areas covered The present review article recapitulates the clinical development of margetuximab, critically discussing its implications in the current landscape of BC treatment algorithms. Expert opinion The clinical role of Margetuximab can only be interpreted in view of the rapidly evolving treatment landscape for pretreated HER2-positive advanced BC. Indeed, the recently approved anti-HER2 agents tucatinib and trastuzumab deruxtecan currently represent appealing options for the post-TDM1 setting, while margetuximab may have a role after progression to the abovementioned agents, in case of a future approval. Regardless of its clinical uptake, it should be noted that the development of margetuximab has relevantly improved our biological understanding of HER2-positive BC, highlighting the implication of patient’s genotype in determining treatment outcomes, as well as the relevance of antibody-dependent cellular cytotoxicity (ADCC) in the context of HER2-blockade.
Highlights
No specific standard treatment is currently recommended for HER2-positive advanced breast cancer (BC) patients progressing to dual HER2 blockade and to trastuzumab emtansine (TDM-1)
Several traditional options are suggested by the HER2 pathway has radically changed the prognosis of this current guidelines, including chemotherapy combined with trassubgroup of patients in the last decades, both in the early and tuzumab, with lapatinib, or a chemo-free treatment with the two advanced setting [2,3]
HER2 ADC trastuzumab deruxtecan [5] and the anti-HER2 tyro- A second TKI was approved by FDA in the same setting, namely sine kinase inhibitors (TKIs) tucatinib [6] and neratinib [7] were neratinib combined with capecitabine, the regimen did recently approved by FDA, enlarging the treatment arsenal of not show to improve survival compared with lapatinib and capepretreated HER2-positive BC patients[4]
Summary
About 15–20% of breast cancers (BC) overexpress HER2 as con- As previously mentioned, a standard treatment strategy for BC. HER2 ADC trastuzumab deruxtecan [5] and the anti-HER2 tyro- A second TKI was approved by FDA in the same setting, namely sine kinase inhibitors (TKIs) tucatinib [6] and neratinib [7] were neratinib combined with capecitabine, the regimen did recently approved by FDA, enlarging the treatment arsenal of not show to improve survival compared with lapatinib and capepretreated HER2-positive BC patients[4]. Among these emerging citabine[7]. The recommended dose, used for the subsequent studies, was 15 mg/kg Q3W or 6.0 mg/kg QW
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