Margetuximab for the treatment of HER2-positive metastatic breast cancer

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.

Automated summary

The novel anti-HER2 agent margetuximab has demonstrated a slight improvement in progression-free survival compared to trastuzumab when combined with chemotherapy for pretreated HER2-positive advanced breast cancer. Its clinical role in the rapidly evolving landscape of HER2-positive breast cancer treatment should be considered in view of other emerging anti-HER2 agents. The development of margetuximab has significantly improved our biological understanding of HER2-positive breast cancer, emphasizing the importance of patient genotype and antibody-dependent cellular cytotoxicity in HER2-blockade context.