A new, highly sensitive test for the HER2 protein could significantly increase the number of lung cancer patients who may benefit from trastuzumab deruxtecan (T-DXd), a recently FDA-approved chemotherapy. The study, published in Modern Pathology, highlights the potential of this novel assay to identify a larger subset of patients with adequate HER2 expression to qualify for T-DXd treatment.
Current HER2 Testing Limitations
While HER2 is a well-established biomarker in breast cancer, its prevalence in lung cancer, as detected by current tests, has been reported to be much lower, around 2%. This has limited the use of HER2-targeted therapies like T-DXd in lung cancer. David Rimm, MD, PhD, Anthony N. Brady Professor of Pathology at Yale School of Medicine, and his team recognized that existing tests, designed for the high HER2 overexpression seen in breast cancer, might not be sensitive enough to detect clinically relevant levels in lung cancer.
"The original test is kind of like a scale for weighing elephants, and we were trying to weigh mice on it," Rimm explained, highlighting the need for a more sensitive assay tailored to the lower HER2 expression levels in lung cancer.
A More Sensitive Approach
To address this, Rimm and his colleagues developed a new test with enhanced sensitivity to detect lower levels of HER2 protein in lung cancer tissues. The team tested their assay on a collection of tissues from 741 lung cancer patients collected over several years at Yale and in Greece. The study detected elevated levels of HER2 in 63% of these lung cancers—enough that those patients could have qualified to receive T-DXd.
This finding suggests that a significantly larger proportion of lung cancer patients could potentially benefit from T-DXd than previously estimated. The increased sensitivity of the new test allows for the identification of patients who might have been missed by standard assays.
Implications for Personalized Medicine
The development of this more sensitive HER2 test represents a step forward in personalized medicine for lung cancer. By accurately identifying patients with clinically relevant HER2 expression, clinicians can better select individuals who are likely to respond to T-DXd, while avoiding unnecessary treatment and potential side effects in those who are unlikely to benefit.
"Come back to me in three to five years and I think it’ll be a common thing to determine which tag is the highest level, so you can pick that drug first," Rimm noted, envisioning a future where comprehensive biomarker testing guides treatment decisions in cancer care.
Future Directions
While the new HER2 test is currently available as a lab-developed test, the team is working towards FDA approval. Additionally, they are exploring the development of similar sensitive assays for other cancer types and biomarkers, with the goal of expanding the application of personalized medicine across a broader range of malignancies. With around 700 drugs, such as T-DXd, are currently in clinical trials, clinicians might be able to test not just HER2 but a range of targets to see which cancer drug to use.
