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SABCS 2021 | Highlights from SABCS 2021: T-DXd, KEYNOTE-355, PADA-1 & EMERALD

Peter Schmid, MD, PhD, FRCP, Barts Cancer Institute, London, UK, provides an overview of the latest treatment updates in breast cancer from the San Antonio Breast Cancer Symposium, including DESTINY-Breast03 (NCT03529110) which demonstrated the superiority of trastuzumab deruxtecan in patients with HER2+ advanced breast cancer, as well as the agents activity in patients with brain metastases. Prof. Schmid discusses the final results from the KEYNOTE-355 (NCT02819518) study presented at the San Antonio meeting evaluating pembrolizumab in advanced triple-negative breast cancer, as well as the PADA-1 study (NCT03079011) which investigated first-line aromatase inhibitor plus palbociclib with randomized switch to fulvestrant plus palbociclib upon detection of circulating ESR1 mutation in hormone-receptor-positive, HER2-negative metastatic breast cancer. This interview took place at the San Antonio Breast Cancer Symposium 2021 in San Antonio.

Transcript (edited for clarity)

I think if you look at metastatic breast cancer, clearly one highlight is the data from the DESTINY-Breast03 trial, which we had already seen at ESMO, and which clearly shows superior efficacy of the HER2-targeting ADC T-DXd, compared with T-DM1. I was impressed, looking at the brain metastasis data, which we are presented here as well, showing that T-DXd has substantial activity in patients with brain metastasis, and providing, essentially, a similar benefit to the overall cohort...

I think if you look at metastatic breast cancer, clearly one highlight is the data from the DESTINY-Breast03 trial, which we had already seen at ESMO, and which clearly shows superior efficacy of the HER2-targeting ADC T-DXd, compared with T-DM1. I was impressed, looking at the brain metastasis data, which we are presented here as well, showing that T-DXd has substantial activity in patients with brain metastasis, and providing, essentially, a similar benefit to the overall cohort. If you go outside HER2-positive disease, we have in HER2 lower again interesting emerging data in an intriguing small study from the French group looking at T-DXd in that setting, showing activity even in HER2 zero patients, which may be down to how HER2 expression is assessed and changes over time.

In triple negative breast cancer, we saw in the first-line setting, important data from the KEYNOTE-355 trial, long-awaited overall survival data demonstrating a substantial benefit from the addition of an immune checkpoint inhibitor first-line chemotherapy. Now also providing more data with three different chemotherapy backbones and giving us some insight in the biomarker work, in terms of showing that the benefit is only seen in patients with a CPS score of 10 or higher, and not with lower CPS scores.

We saw in ER-positive breast cancer, really interesting academic French study which I would like to bring attention to. There’s a trial for patients with first-line metastatic breast cancer, endocrine therapy, aromatase inhibitor and a CDK4/6 inhibitor. And those patients underwent serial blood assessments for possibly emerging ESR1 mutations. There was a group of patients where a clone was detected with ERS1 mutations, but the patients didn’t have progressive disease and those patients were randomized to either continue with the current treatment with aromatase inhibitor and CDK4/6 inhibitor, or be switched to Fulvestrant, that’s a different endocrine backbone with CK4/6 inhibitors. And that switch in endocrine therapy before patients have progressive disease doubled progression-free survival from around 6 to 12 months, which I think is a really intriguing result and warrants further investigation.

Finally, we saw the first phase III data of a trial with an oral SERD, and in the EMERALD study we saw, and I think it’s important from a proof of principle point of view, we saw that an oral SERD provides superior efficacy compared to Fulvestrant aromatase inhibitors in patients who had prior CDK4/6 inhibitor therapy. This is obviously a relative resistant group of patients and so the absolute PFS is small. But if you look at the hazard ratio in all patients 0.7 and 0.55 in patients with ESR1 mutations, it provides important proof of principle of the value of these SERD compounds, which are now also moving into the adjuvant setting.

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