At the 2022 San Antonio Breast Cancer Symposium, Aditya Bardia, MD, Massachusetts General Hospital, Boston, MA, presented results from the phase 2 TRIO-US B-12 TALENT trial, examining the efficacy of neoadjuvant trastuzumab deruxtecan for patients with HER2 low, HR-positive early-stage breast cancer.

Dr Bardia discussed the need for alternative treatments for patients with HER2 low breast cancer, as the current standard of care has low pathological complete response rates (pCR) and significant toxicity. He noted, in this trial, trastuzumab deruxtecan improved pCR rates in patients and reduced toxicity, justifying further studies of this line of treatment for HER2 low breast cancer.

Transcript

I'm Aditya Bardia, Breast Medical Oncologist at Mass General Cancer Center, Harvard Medical School, Boston. At the San Antonio Breast Cancer Symposium 2022, we saw the results of the TALENT trial. As a reminder, the TALENT trial evaluated trastuzumab deruxtecan for patients with hormone receptor-positive HER2 low breast cancer in the neoadjuvant setting. As a brief background, patients with high-risk hormone receptor-positive HER2-negative breast cancer often receive neoadjuvant anthracycline/taxane-based chemotherapy. However, the pathological complete response rate is low, 5% or so. Objective radiological response rate is about 50%, and it can be associated with significant toxicity, including dose interruptions or reductions, as well as side effects like cardiomyopathy, neuropathy, and risk of leukemia. Clinically, there's an unmet need for better therapies in this setting. Trastuzumab deruxtecan, a HER2-directed antibody drug conjugate, has demonstrated activity in hormone receptor-positive HER2 low metastatic breast cancer.

We designed the TALENT trial to evaluate trastuzumab deruxtecan in early breast cancer as a neoadjuvant therapy. In terms of study design, it was a trial for patients with high-risk hormone receptor-positive HER2-low breast cancer. Early-stage patients were randomized to receive trastuzumab deruxtecan or trastuzumab deruxtecan plus anastrozole. Patients were enrolled at multiple centers in the United States. Overall, we saw a radiological response rate with trastuzumab deruxtecan alone of 68%, and with trastuzumab deruxtecan plus anastrozole of 58%, including 2 complete responses. We also looked at change in HER2 expression from baseline to surgery after treatment with trastuzumab deruxtecan, and for several patients, you could see decrease in HER2 expression with trastuzumab deruxtecan. Finally, we see a pCR rate combined with near pCR – residual cancer burden (RCB) 0 and 1 combined – of 15% with trastuzumab deruxtecan.

In terms of safety, this is an early look at the data. The number one side effect seen with trastuzumab deruxtecan was nausea. The rate of dose reduction or discontinuation was low, about 5%, which is much lower than what we see with standard chemotherapy. We didn't see side effects like cardiomyopathy with trastuzumab deruxtecan. There was 1 patient who had grade 2 pneumonitis with trastuzumab deruxtecan, but no cases of grade 3 or grade 4 pneumonitis. Finally, we looked at whether the incidents of side effects changed over time. We looked at the first 20 patients who were enrolled, the next 20, and then the last 18. You could see that for the gastrointestinal (GI) side effects, the incidents decreased over time. This highlights the fact that investigators became more comfortable with supportive therapy, so the incidence of these GI adverse events decreased.

Overall, this is the first trial looking at neoadjuvant trastuzumab deruxtecan. It demonstrates preliminary evidence of clinical activity and a toxicity profile that we've seen before, and essentially lays the groundwork for future studies with antibody drug conjugates, as single agent or combination therapy, for patients with early-stage breast cancer.

Source:

Hurvitz SA, 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