The availability of more potent HER2-targeted therapies, such as antibody-drug conjugates (ADCs) like fam-trastuzumab deruxtecan (T-DXd), has the potential to revolutionize the treatment landscape for patients with lower levels of HER2 expression, including those in the HER2-low and HER2-ultra low categories. These therapies offer a new paradigm in HER2-targeted treatment by delivering potent cytotoxic agents directly to HER2-expressing cells, regardless of the level of HER2 expression.
For patients with lower levels of HER2 expression who may not have qualified for traditional HER2-targeted therapies in the past, these more potent ADCs provide a promising treatment option. The ability of ADCs to induce a bystander effect, where the cytotoxic payload can affect neighboring cells, expands the therapeutic potential beyond the direct targeting of HER2-positive cells. This mechanism of action may be particularly beneficial in tumors with lower levels of HER2 expression, where traditional HER2-targeted therapies may have been less effective.
The introduction of these more potent HER2-targeted therapies could lead to a shift in treatment decision-making for patients with lower levels of HER2 expression. Clinicians may now consider these patients as candidates for HER2-directed therapies, even if they fall into the HER2-low or HER2-ultra low categories. This expanded treatment landscape offers new hope for patients with HER2-low breast cancer and underscores the importance of reevaluating treatment strategies based on the availability of novel and more effective therapies.