At the 2022 San Antonio Breast Cancer Symposium, Sara Hurvitz, MD, David Geffen School of Medicine – UCLA, Los Angeles, California, presented preliminary results from the TRIO-US B-12 TALENT trial, investigating the efficacy of trastuzumab deruxtecan, either alone or in combination with anastrozole, given prior to surgery for hormone receptor-positive, HER2 low, early-stage breast cancer.

This preliminary data from the trial showed a benefit to overall response rate for patients who were treated with trastuzumab deruxtecan alone when compared with trastuzumab deruxtecan and anastrozole.

Transcript:

I am Dr. Sarah Hurvitz, professor of medicine at the UCLA David Geffen School of Medicine, Johnson Comprehensive Cancer Center. And here at the San Antonio Breast Cancer Symposium, my colleague and I presented the TRIO-US B12 TALENT clinical trial. This is a clinical trial that was aimed to look at the activity and safety of trastuzumab deruxtecan [T-DXd], either alone or in combination with anastrozole for early-stage breast cancer that was hormone receptor-positive (HR+) and HER2-low expressing.

We know HR+, HER2 non-amplified breast cancer has a low chance of pathologic complete response and a lot of toxicity associated with standard-of-care multi-agent chemotherapy. We wanted to evaluate the activity of trastuzumab deruxtecan in HER2 low, HR+ breast cancer when given prior to surgery in stage 2 or 3 disease. The DESTINY-Breast04 clinical trial showed very good activity of trastuzumab deruxtecan in HR+, HER2 low metastatic breast cancer. This, however, is the first study looking at early-stage breast cancer.

We showed that the objective response rate (ORR) associated with trastuzumab deruxtecan in patients treated with trastuzumab deruxtecan alone was about 68%. When trastuzumab deruxtecan was combined with anastrozole, the ORR was about 58%. We also began to get early indicators of the pathologic responses seen in our first patients who completed therapy on this trial. We saw 1 patient have a complete pathologic response, and 4 patients in the study have a near pathologic response, but we're still waiting for several patients to complete therapy and complete surgery.

We also were able to evaluate the expression levels of HER2 by immunohistochemistry and changes from baseline prior to treatment after a cycle of therapy and at the time of surgery. This showed some interesting changes that were detected by immunohistochemistry staining for HER2 expression level.

I think at our next reporting, we'll have all the patient data. All the patients will have completed their neoadjuvant therapy, 6 to 8 cycles of trastuzumab deruxtecan with or without the anastrozole. We'll have that pathologic complete response rate data, but we're also going to have a rich biomarker dataset to look at in terms of Ki-67 changes, HER2 expression level, ctDNA, et cetera. Stay tuned next year for those data. I do think these data are important. Although they're preliminary, I think they're very important because they are going to inform the direction that we take when we're evaluating trastuzumab deruxtecan in early-stage HR+, HER2 low breast cancer.

Source:

Hurvitz S, Bardia A, Press MF, et al. “TRIO-US B-12 TALENT: Neoadjuvant trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early stage breast cancer.” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS2-03