VIDEO: New therapies will ‘change the landscape’ of ER-positive breast cancer

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The field of new and novel endocrine therapies is rapidly expanding, and we have a series of new agents, including SERDs and new SERMs as well. And it's a never-ending list of acronyms these days with PROTACs and SERMs, you know, but very exciting time. I think this is going to change the landscape of ER-positive breast cancer significantly, considering that most of the progress that had been made in the recent past in endocrine therapy had really been on partners to endocrine therapy, such as the drugs that we just talked about, you know, P3CA targeting, or CDK-46 inhibitors, mTOR inhibitors, and others. But really we have not had any major changes in the endocrine therapy backbone.

You know, we've been treating patients with tamoxifen, aromatase inhibitors and fulvestrant (Faslodex, AstraZeneca) now for quite some time. So the SERDs are kind of the first new change to the endocrine therapy backbone. What's unique about these drugs is that they appear to be more effective, perhaps more potent than the currently available SERM, which is fulvestrant. And in addition to that, they have the advantage of being oral, for the most part, whereas fulvestrant is an intramuscular injection, with a few limitations about that.

Currently we have elacestrant (Orserdu, Stemline Therapeutics), which is FDA approved for patients with ESR1 mutation. So that's already available, and we see that that can benefit patients, you know, particularly with ESR1 mutations, which previously didn't have any viable targetable treatments, but particularly benefiting patients that have endocrine-sensitive disease and have received a CDK-46 inhibitor and benefited from it for at least a year, we see that that subset of patients is benefiting quite a bit. But as the ongoing research matures, I think what I'm excited about these agents is the potential for them as combination therapy.

So we know that a single agent, particularly after CDK-46 inhibitors, these agents appear to have somewhat limited activity. But when we start combining them, you know, with some of our currently available targeted therapies, that's where I think they may shine and help a lot of our patients. So there's combinations with CDK-46 inhibitors or treatments after CDK-46 inhibitors, essentially replacing fulvestrant potentially in the future. And then these agents are also being evaluated in the adjuvant setting.

So for patients with curable resectable breast cancer, they are being tested against our routinely available adjuvant therapies, either as an upfront strategy where you test these new SERDs against, you know, tamoxifen or regular aromatase inhibitors, or as a switch strategy where you can treat patients adjuvantly for a few years, and then transition to these new SERDs for the remainder of their treatment.