Liquid Biopsy May Predict T-DXd Activity in HER2+ Metastatic Breast

Paolo Tarantino, MD spoke with CancerNetwork^® during the 2023 San Antonio Breast Cancer Symposium (SABCS) about real-world findings from the RELIEVE study that highlight how testing for HER2 status with a liquid biopsy assay may more accurately predict the clinical activity of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with metastatic breast compared with a standard immunohistochemistry assay.

Tarantino, a medical oncologist at Dana-Farber Cancer Institute, also described how outcomes for patients with ERBB2 deletions differed from those of the rest of the study population. In the study, 10.3% of patients with available next-generation sequencing data had an ERBB2deletion, whose median time to next treatment was 4.1 months compared with 7.6 months in those without a deletion (P = .41).

Transcript:

It was very intriguing to see this difference in the activity of T-DXd based on changes in HER2 status. But at the same time, these changes that were reflected in our study were based on immunohistochemistry. That is the current method we used to test for HER2, but it’s not the best. We know that it has high discordance among pathologists and it’s not ideal in the low ranges. This is why we also conducted additional analysis in our study. It’s important to expand the way we look at HER2.

We looked at it with a liquid biopsy test called DNADX from plasma collected before T-DXd treatment. And we found that a HER2 signature based on this liquid biopsy was able to predict the activity of T-DXd, and that was very promising. And then we looked at genetic aberrations or ERBB2 deletions; 10% of the patients had these deletions in our study. They seem to have a shorter time next treatment of 4 months instead of more than 7 months for the rest of the population.

We’re still looking at [the data]. I think that what the study tells us is that we need to keep looking at different assays beyond immunohistochemistry because we can improve the prediction of T-DXd activity. We really need to do that because we’re having more and more agents in the space, and in the future, we’ll need to select the patients more appropriately than we’re doing today.

Reference

Tarantino P, Hughes M, Kusmick R, et al. Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE). Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; abstract PS08-09.