VIDEO: Precision medicine ‘evolving’ in metastatic breast cancer

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I think we were lucky to see at least four approvals by the FDA for metastatic breast cancer that really have reshaped practice in recent years. And two in particular have reshaped practice for chemotherapy-pretreated metastatic breast cancer, and these are the two antibody drug conjugates T-DXd, or trastuzumab deruxtecan [Enhertu; Daiichi Sankyo/AstraZeneca, and sacituzumab govitecan [Trodelvy; Gilead]. And both of them are meant to deliver topoisomerase inhibitors in a more selective way and effective way to cancer cells. T-DXd was tested in the DESTINY-Breast04 trial that showed overall survival improvement, both for hormone receptor-positive and triple-negative metastatic breast cancer. And sacituzumab govitecan was also tested, both in triple-negative disease in the ASCENT trial and HR-positive disease in TROPiCS-02, both showing overall survival improvement. So, ADCs have really helped to treat patients with chemotherapy-pretreated metastatic breast cancer. But two other approvals have actually reached an earlier setting in ER-positive breast cancer. So, elacestrant [Orserdu; Menarini Group] was the first novel endocrine treatment to be approved in in over 20 years and it's basically a novel SERD, degrader of the estrogen receptor. And it is oral and so it has a better, let's say, an easier formulation compared to fulvestrant [Faslodex; AstraZeneca] that was injective, and has shown, actually, improvement in progression-free survival compared to fulvestrant and other endocrine treatments in the EMERALD phase III trial. And it's now approved for patients that have ESR1-mutant metastatic breast cancer. And finally, capivasertib (Truqap; AstraZeneca]. Capivasertib is the first AKT inhibitor to be approved for metastatic breast cancer, and was approved in combination with fulvestrant for patients that have alterations in AKT, PIK3CA, or p10. So in general, I think we're seeing an expanding arsenal. Some of these agents are approved based on specific biomarkers like T-DXd for HER2-low breast cancer, capivasertib, AKT, p10, and PIK3CA mutant breast cancer, and elacestrant for ESR1-mutant breast cancer, which I think makes it more and more important to look at these alterations with pcDNA3 or NGF. And so, I think precision medicine in breast cancer is really evolving.