Margetuximab for the treatment of HER2-positive breast cancer

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Published: 12 Jun 2019
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Prof Debu Tripathy - The University of Texas MD Anderson Cancer Center, Houston, USA

Prof Debu Tripathy speaks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about an abstract that was presented at this year's meeting that could potentially change breast cancer practice.

He discusses the use of the HER2-directed antibody, margetuximab that has been specifically engineered to have a high affinity for the Fc receptor. This trial compared the effect of this antibody with trastuzumab, both in combination with chemotherapy.
 

 

Several other abstracts are important and may change practice. The one that is really new and is being presented for the first time is with a new antibody called margetuximab. This is an antibody directed against HER2, the human epithelial receptor 2. For the last twenty years now we have had more effective therapies for the 20% or so of patients that have HER2 positive breast cancers. Trastuzumab, also known as Herceptin, was introduced at that time and actually prolongs survival both in early and late stage disease.

However, in patients with advanced breast cancer, despite the numerous therapies that have since been approved, patients do ultimately become resistant to these therapies. So we need newer treatments. We’ve also known for many years that the effects of antibodies like trastuzumab are based not only on blocking the growth factor function of HER2 but also on stimulating the immune system. Some people inherit different versions of receptors to the antibodies that activate the immune system, these are known as Fc receptors. Some people inherit low affinity receptors that makes them get less of the benefit from treatments like trastuzumab.

Margetuximab is an antibody that has been engineered, the amino acids have been changed, to have a higher affinity for the Fc receptor. So it’s a very elegant design and the question was will this new engineered antibody perform better than trastuzumab and other chemotherapy drugs which they are typically given with. So this trial compared margetuximab plus chemotherapy of physician’s choice to trastuzumab plus chemotherapy of physician’s choice in patients who had already progressed on all the standard therapies. This study, in fact, did meet its endpoint, it showed an improvement in progression free survival of about a month. We typically like to see longer improvements but nevertheless this did meet the pre-specified threshold and was statistically significant.

In addition, patients on margetuximab had a higher response rate. So we await longer follow-up of this study, including survival and other safety signals. So far it appears to be as safe as trastuzumab and this represents a new option for patients with HER2 positive breast cancer. But also, perhaps more importantly, the theory that one can actually alter the antibody to bind and affect other activities of the immune system is a very important step and perhaps this will be employed in other adaptations and design modifications to currently available antibodies across a whole spectrum of diseases.