Why is macituximab/magenex used late?

HER2-positive breast cancer is one of the most mature cancer types with currently targeted therapy systems. A variety of mature drugs including trastuzumab, pertuzumab, T-DM1, and T-DXd have been widely used. Front-line treatment usually prioritizes the use of classic combinations with extensive clinical experience because of their stable efficacy, high predictability, and clear tolerability profile. If a new drug has a similar mechanism of action to a traditional regimen, it will often not directly replace the existing standard, but will supplement it in the post-drug resistance stage.

The emergence of margetuximab is designed to address the shortcomings of existing HER2-targeted drugs. After long-term use of traditional antibodies, the immune system response efficiency of some patients decreases, weakening the antibody-dependent immune clearance ability. Margetuximab structurally enhances the binding of Fc to immune cells, thus making up for the shortcomings of traditional antibodies in immune response. Therefore, its positioning is naturally placed in the scenario of "after the failure of traditional solutions" to provide new treatment paths.

Overseas information also mentioned a key point: the research and development direction of new HER2 drugs is shifting from "blocking signaling pathways" to "enhancing immune responses", and margituximab is the product of this concept. Immune-enhancing antibodies are usually more suitable for intervention at the metastatic stage when tumor burden is higher and immune evasion ability is stronger, because at this time the immune system needs additional stimulation to effectively eliminate cancer cells.

In addition, international treatment guidelines usually reserve new drugs for later use, also to allow patients to have more "treatment gradients" throughout the disease process. Once too many new drugs are used on the front lines, there will be a lack of alternatives later. From an economic and accessibility perspective, the cost and availability of new drugs also make it more suitable to be placed in the stage after rigorous evaluation by doctors.

Reference materials:https://www.margenza.com/