Metastatic Breast Cancer Video Perspectives
Sara M. Tolaney, MD, MPH
Tolaney reports consulting or advising for Aadi Biopharma, ARC Therapeutics, Artios Pharma, AstraZeneca, Bayer, Blueprint Medicines, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo, Eisai, Eli Lilly, Genentech/Roche, Gilead, Jazz Pharmaceuticals, Incyte Corp, Infinity Therapeutics, Natera, Menarini/Stemline, Merck, Myovant (now Sumitovant Biopharma), Novartis, OncXerna, Pfizer, Reveal Genomics, Sanofi, Seattle Genetics, Umoja Biopharma, Zentalis, Zetagen and Zymeworks; and receiving research funding from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Exelixis, Genentech/Roche, Gilead, Lilly, Merck, NanoString Technologies, Novartis, OncoPep, Pfizer and Seattle Genetics.
VIDEO: 'Exciting' areas of research in metastatic breast cancer
Transcript
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There's lots of areas that seem particularly exciting to me in metastatic disease. I will say maybe I'm a little biased, but one area that I'm very excited about are the antibody-drug conjugates, and the reason I think this leads me to be excited is that these agents have really allowed us to get very high doses of chemotherapy into cancer cells, and we're seeing that they are really changing outcomes. You know, particularly when you look at T-DXd, we are seeing dramatic shifts in survival with the introduction of T-DXd, and I think the other exciting thing is it's allowed us to kind of break free from the way we've done drug development. We've sort of pocketed development into these, you know, drugs for ER-positive disease, for HER2-positive disease, for triple-negative breast cancer, but in fact, T-DXd works across all subtypes really just because there's a little bit of that target of HER2 around, and then the drug is able to work.
And so it's sort of teaching us that maybe you don't need to find an oncogenic driver for the cancer. We were so used to saying, "Hey, if the PI3 kinase pathway is activated, we need to turn off that pathway, or, "HER2 is driving the cancer in metastatic HER2 positive disease, we need to turn off that driver." But maybe if you can just find a target that's just prevalent across the cancer cells, even if it's not driving the cancer to grow, that becomes an easy way to target the cancer.
And now there are a bunch of new antibody-drug conjugates in development, things like datopotamab deruxtecan (AstraZeneca, Daiichi Sankyo), patritumab deruxtecan (HER3-DXd, Daiichi Sankyo), disitimab vedotin (RC48x, RemeGen), ARX788 (Ambrx), all these really cool ADCs. And so I do think it is really going to change things for us. And I think, hopefully, in the early breast cancer space, maybe these ADCs will allow us to replace part or all of chemotherapy, and so that could have dramatic impact on outcome as well.
