Sara A. Hurvitz, MD: New Findings on Neoadjuvant Trastuzumab Deruxtecan and Anastrozole in Early-Stage Breast Cancer

The TRIO-US B-12 TALENT Clinical Trial was a study aimed to investigate the activity of TDXD, either alone or in combination with endocrine therapy in hormone receptor positive HER2 low breast cancer in the neoadjuvant or curative setting. So treating patients prior to surgery. Why is this important? We know that patients with hormone receptor positive breast cancer treated with neoadjuvant therapy have a very low chance of achieving a pathologic complete response, and even a low chance of a good objective response to therapy, even with multi-agent chemotherapy or CDK-46 inhibitors and endocrine therapy we're not getting great outcomes. TDXD has demonstrated significant benefits in the metastatic hormone receptor positive, HER2 low phase from the Destiny Breast 04 clinical trial, but has not yet been tested in the early stage setting in hormone receptor positive HER2 low disease. So we conducted a very early phase, phase two clinical trial where patients were treated with TDXD alone or with TDXD with anastrozole. Patients had to have stage two or three early stage breast cancer that was ER positive and had to have centrally confirmed HER2 low expression. We evaluated patients and then treated them with six cycles of TDXD, either alone or with anastrozole. And then after we enrolled about half the patients and began to see some near pathologic complete responses, we amended the protocol and extended the length of therapy to eight cycles. We presented at San Antonio our interim data, very preliminary evidence of activity and our observations of how this drugs or drugs work together in this setting. We showed that there was an objective response rate of 68% with TDXD alone and 58% of TDXD plus endocrine therapy from baseline to the time of surgery. So this is an objective response rate. It's important to note the denominator includes patients who haven't yet completed therapy or who came off therapy early. This objective response rate is somewhat kind of like what we saw in the Destiny Breast 04 clinical trial. We also saw one patient have a pathologic complete response, and we saw an additional four patients have a near pathologic complete response in RCB one. So the data are very intriguing. We are still waiting for surgical results from 24% of the patients treated with TDXD and 31% of the patients treated in the combination arm. So it's too early to call a PATH CR rate. But the data that we got, it's very intriguing. It's interesting, and it is allowing us to look at the biomarkers, what's happening to HER2? What's happening in the tumor microenvironment as we treat with TDXD, with or without endocrine therapy. Next year, we plan to report the final results, and I think these results may help inform the design of studies of TDXD in the early stage setting for HER2 low disease.