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Promising findings from various clinical trials at the San Antonio Breast Cancer Symposium (SABCS) have the breast cancer research community buzzing about the future of treatment in metastatic disease. As we close out 2022, what are some of the most exciting therapies we should expect to change practice in 2023?

In this exclusive 名媛直播 video, , professor of medicine and director of the Breast Cancer Center at NYU Langone Health's Perlmutter Cancer Center in New York City, offers her take on the landscape of potential future treatments in metastatic disease.

The following is a transcript of her remarks:

So let's talk about metastatic breast cancer. It is still a fatal disease. However, in most subtypes now there's been dramatic progress in terms of survival improvements after new therapies have come to clinical trials and to the market.

So for instance, in HER2-positive breast cancer, probably the most exciting year has been the last year, with the data showing that antibody-drug conjugates really prolong survival compared to other therapies, including other antibody drug-conjugates, but also the effort now to move them into earlier lines of metastatic treatment. So an update from [DESTINY-Breast03] showed that the progression freedom from T-DXd or trastuzumab deruxtecan [Enhertu] is much improved compared to the current standard of care of T-DM1 [trastuzumab emtansine] or Kadcyla. So that is a major advance in the field, because now compared to Kadcyla, which has for instance 7 months of freedom from progression, now we have 29 months freedom of progression. That is a very, very large difference. And in that study, the median overall survival hasn't been reached, but there's a clear difference between the two arms as well.

So I think that just now really cements the role of T-DXd in the second-line setting for most patients. And obviously there is the toxicity that we are worried about, the interstitial lung disease [ILD], and patients need to be monitored very closely and [if there's] any signs of potential ILD we need to stop the medication and go from there. But this is the update for HER2-positive disease.

In triple-negative disease, I think a couple years ago now we had approval of chemo-immunotherapy for patients with PD-L1 positive tumors. We also now have the approval of immunotherapy in the neoadjuvant setting for pretty much every stage II and III triple-negative breast cancer.

So I think in the future we'll need to find out if immune therapy in patients who had been exposed to immunotherapy in the curative setting is meaningful, with meaningful benefit to patients, or if we need to change our strategies for these women.

But we know we have sacituzumab [Trodelvy] in metastatic triple-negative disease approved. But now also there is a new option for patients who fall into the category of HER2-low tumors. And, and this is about like a third of the patients who have [triple-negative breast cancer] that have tumors with HER2-low expression. And nowadays these patients qualify for Enhertu, or also T-DXd. And in the studies, that's actually been very promising. So regardless of the degree of HER2 expression -- [IHC] 1+ versus 2+ -- we've seen the results are very, very similar. So this is now a treatment option as well for patients who have triple-negative breast cancer.

For women and men who have [estrogen receptor]-positive metastatic breast cancer, there is soon to be a new option available. A study shown here at the San Antonio Breast Cancer Symposium, looked at an AKT inhibitor given to patients after they had received already one line of endocrine therapy. And this was given in combination with fulvestrant [Faslodex], currently our second-line standard of care. And in this study, there was a signal for significant improvement in [progression-free survival]. So there was doubling of progression-free survival for patients if they received capivasertib. And this was seen in all-comers, in all patients, but also to a very similar degree in patients who had alterations in pathways of AKT such as PI3-kinase, P10, and AKT.

And if the overall survival data -- this was an immature look at the overall survival curves, and there's already a significant separation visible -- but once those data are clear, and I expect the drug would be approved, we actually would have a very different option for patients in the second-line setting, because currently after CDK failure, these patients usually we test their tumors for PI3-kinase mutations, and then there is an FDA approved drug for the PI3-kinase-mutated tumors. However, there's lots of side effects with that therapy, including hyperglycemia, which is quite difficult to manage. So if we were able to have a more tolerable drug that also affects these PI3-kinase-mutant tumors, that would be a major win. And in fact, the data from from today's presentation show that the efficacy was seen across the board, even in patients with wild type tumors in these pathways. So I'm very excited about this potential new category of drugs to be incorporated into our armamentarium.

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