Potential Role for T-DXd in Early-Stage HER2-Low Breast Cancer


Panelists share a brief discussion on early-stage HER2-low breast cancer and identify treatment options available in that setting.


Aditya Bardia, MD, MPH: How about early breast cancer? Do we have any data related to T-DXd [trastuzumab deruxtecan]? In early breast cancer, Sara, you led the TALENT trial, which was an IST looking at T-DXd in early hormone receptor–positive, HER2-low breast cancer. Could you review the study and future directions?

Sara A. Hurvitz, MD: And you presented it so well at San Antonio [Breast Cancer Symposium]. As you said, this was an IST that was proof of concept. It was a very small trial aimed to evaluate whether the use of T-DXd in this setting may help bud the pathologic complete response [CR] rate that is so low when we use standard chemotherapy or endocrine-based therapy in the neoadjuvant setting for hormone receptor–positive breast cancer. We wanted to interrogate whether using T-DXd alone or in combination with endocrine therapy would be effective, safe, as well as use the opportunity of the neoadjuvant setting to take tissue and blood to do some biomarker work. We presented very early data from this study. Patients in arm A received T-DXd alone, and in arm B, T-DXd with anastrozole. Patients had a biopsy at baseline after a cycle of therapy and at the time of surgery. Initially, the study was conducted to do 6 cycles of therapy then go to surgery. But when we started seeing near pathologic CRs after discussion among all the investigators, we decided to push it to 8 cycles.

The patients who were selected for this study would generally be selected to receive chemotherapy. In other words, these were higher-risk patients, over half of them had node-positive disease. They had higher Ki67—over half of them had a Ki67 of 30% based on central assessment. And very few patients had grade 1 tumors. Interestingly, we showed that the objective response rate was around 68% based on imaging at baseline in the time of surgery in the T-DXd alone arm and was about 58% in the T-DXd with endocrine therapy arm. We also saw that HER2 expression does appear to change, based on central assessment of baseline and at the time of surgery, which was getting to Virginia's earlier point that there's this possibility of dynamic changes of HER2, especially when exposed to HER2-targeted therapy with downregulation seen more commonly than upregulation and in expression.

We only observed 1 patient who had a pathologic CR, and that was in the single-agent arm, but there were 5 patients who achieved a near pathologic CR. Because people were expecting us to have final data presented, it’s important to note that we have about 25% to 30% of the patients who are still awaiting surgery. These data are interesting. They're certainly not practice changing. We're all very eager to see data relating to T-DXd in the adjuvant setting in HER2-positive and HER2-low breast cancer. But this is going to be a lot of fun in terms of the biomarker work that's forthcoming. Hopefully we'll have final data to present toward the end of 2023.

Aditya Bardia, MD, MPH: That would be great. The study provides proof of principle and sets the stage for additional ADC [antibody-drug conjugate]–based studies in early breast cancer.

Transcript edited for clarity.

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