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SABCS 2022 | TALENT: neoadjuvant T-DXd with or without anastrozole for HER2-low, HR+ early stage breast cancer

Trastuzumab deruxtecan (T-DXd) is a novel HER2-targeting antibody drug conjugate (ADC) that is FDA approved in the US for HER2-positive and HER2-low metastatic breast cancer. However, the efficacy of T-DXd in the neoadjuvant setting is not known. Aditya Bardia, MD, Massachusetts General Hospital, Boston, MA, discusses results from the TRIO-US B-12 TALENT (NCT04553770) trial evaluating neoadjuvant T-DXd with or without anastrozole for HER2-low, HR+ early stage breast cancer. Results from stage 1 of the study suggest that T-DXd with/without endocrine therapy demonstrates promising clinical activity for patients with HR+ breast cancer. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2022 in San Antonio, TX.

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Transcript (edited for clarity)

At SABCS 2022, we saw the results of the TALENT trial looking at neoadjuvant trastuzumab deruxtecan with or without anastrozole for patients with high risk hormone receptor (HR)-positive, HER2-low breast cancer. As a brief background, for patients with high risk HR-positive early-stage breast cancer, we tend to use neoadjuvant anthrocycline, taxane-based chemotherapy, but it’s associated with low response rate, pCR rate of about 5%, and can be associated with significant toxicity including myelosuppression, peripheral neuropathy, cardiomyopathy, risk of leukemia...

At SABCS 2022, we saw the results of the TALENT trial looking at neoadjuvant trastuzumab deruxtecan with or without anastrozole for patients with high risk hormone receptor (HR)-positive, HER2-low breast cancer. As a brief background, for patients with high risk HR-positive early-stage breast cancer, we tend to use neoadjuvant anthrocycline, taxane-based chemotherapy, but it’s associated with low response rate, pCR rate of about 5%, and can be associated with significant toxicity including myelosuppression, peripheral neuropathy, cardiomyopathy, risk of leukemia. A number of patients need those reductions as well as interruptions. So clinically there’s an unmet need for better therapies in this setting. Trastuzumab deruxtecan is a novel HER2-directed antibody-drug conjugate that has demonstrated clinical activity for patients with metastatic HR-positive, HER2-low breast cancer, and is FDA approved for that indication.

In the TALENT trial, we evaluated trastuzumab deruxtecan for patients with early-stage HR-positive, HER2-low breast cancer. Patients were randomized to receive trastuzumab deruxtecan alone, or trastuzumab deruxtecan plus anastrozole. In terms of the study results, there are three key findings. The first is that overall, in patients who received trastuzumab deruxtecan alone, the objective radiological response rate was 68% and patients who received trastuzumab deruxtecan plus endocrine therapy, it was 58%. In terms of pCR and near pCR, which is RCB01, that was 15% with trastuzumab deruxtecan alone, and trastuzumab deruxtecan plus anastrozole, it was 15% as well.

And then finally, in terms of safety, nausea was the number one side effect that was seen with trastuzumab deruxtecan. There was one patient who had grade two pneumonitis, but no cases of grade three or four pneumonitis were seen. No cardiomyopathy was seen, and overall 5% of patients needed a dose reduction, and the rate of treatment discontinuation was very low. So overall, the drug was well tolerated in the clinical trial.

So the bottom line is in Talent trial, we saw that neoadjuvant trastuzumab deruxtecan has preliminary evidence of clinical activity and was well tolerated in this setting, and it sets the stage for subsequent ADC-based clinical trials, either as a single agent or in combination therapy for patients with HR-positive early-stage breast cancer.

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