A novel selective biomarker tool (Troplex) may help select which antibody-drug conjugate therapy could be most effective in patients with metastatic breast cancer, according to findings presented by Robbins et al at the 2023 San Antonio Breast Cancer Symposium (Abstract PO3-13-11).
Background
Antibody-drug conjugates are a type of targeted therapy designed to release cancer drugs to specific tumor cells. However, their efficacy often depends on target expression and the best method for measuring expression is still unknown.
The antibody-drug conjugates fam-trastuzumab deruxtecan-nxki (T-DXd) and sacituzumab govitecan were approved by the U.S. Food and Drug Administration to treat patients with metastatic breast cancer.
Study Methods and Results
In the new study, researchers used quantitative immunofluorescence to assess levels of HER2, TROP2, and cytokeratin across hundreds of metastatic breast cancer cases.
The researchers discovered that most of the cases demonstrated high levels of HER2 or TROP2.
“Since the level of target is directly proportional to the likelihood of response, we built an assay that could measure that in a quantitative way,” explained senior study author David Rimm, MD, PhD, the Anthony N. Brady Professor of Pathology and Professor of Medicine (Medical Oncology) at the Yale School of Medicine as well as Director of the Yale Cancer Center Tissue Microarray Facility. “By doing this, we could compare the two and then see which one is higher. If it turns out that TROP2 is expressed at higher levels than HER2, on average, then oncologists may want to start by treating the patient with [sacituzumab govitecan],” he suggested.
Conclusions
The researchers hope their new findings can provide valuable clinical data to physicians selecting between T-DXd and sacituzumab govitecan. In future studies, the researchers plan to apply and evaluate the same quantitative methods with many other pairs of antibody-drug conjugates in the hope of uncovering more selective assays that can be used in clinical settings.
