HR+/HER2- Metastatic Breast Cancer: An Evolving Treatment Paradigm


Closing out his discussion on HR+/HER2- metastatic breast cancer, Kevin Kalinsky, MD, MS, highlights key takeaways and shares excitement for future evolutions in the treatment paradigm.


Kevin M. Kalinsky, MD, MS: So, for patients with hormone receptor–positive, HER2-negative, endocrine-sensitive disease, you can see that this is a really actively interrogated disease at this time. In terms of targeted therapies, the agent that we’re anticipating may get FDA approval next is capivasertib. Again, we’ll see [whether] this is for patients with PI3K/AKT pathway-altered tumors only or for all comers. We’re also awaiting the results of randomized phase 3 trials with CDK4/6 inhibitors. Of course, these are agents that have been approved and we’re familiar with, but there’s a question about sequencing these. We’re waiting for the results of those trials like postMONARCH [NCT05169567]. There are a number of other interesting targeted therapies that are coming down the pipe as well, including PI3K mutant-specific inhibitors, those that do not inhibit wild-type but may inhibit, for instance, H1047R may have less toxicity with significant benefits. I would keep your eyes out for those studies. Those are in early-phase trials at this time on the targeted therapy side. Now we’re on the endocrine therapy side as well. Right now, we have the approval of elacestrant for patients who have ESR1 mutations. We’ll see how the other oral SERDs [selective estrogen receptor degraders] pan out, whether these will be approved in only the mutant population but wild-type as well. Also, categories like CERANs [complete estrogen receptor antagonists], other SERDs, etc. There are lots of things going on. I suspect in the next few years we’ll see how all of this shakes out. It is quite promising because, ultimately, we want to continue endocrine therapy or targeted therapy for as long as possible before we have to introduce chemotherapy or [antibody-]drug conjugates in the metastatic setting.

Kevin M. Kalinsky, MD, MS: So, I think we’re most eagerly anticipating seeing, within the next 6 months or so, the data from DESTINY Breast06 [NCT04494425]. This is a study that’s looking at the potential utility of trastuzumab deruxtecan in a HER2 ultra-low population. Right now, we’re giving it to patients who have HER2 low disease. We’re awaiting the data for patients with ultra-low disease, asking the question of whether we should be utilizing trastuzumab deruxtecan in even more patients with breast cancer. In ASCO this year, we saw the results of the benefit of trastuzumab deruxtecan and various other malignancies in patients just demonstrating the activity of this drug. In breast cancer, the question is whether we can go even lower, where if you have just a little bit of HER2 expression, whether you benefit from getting the drug.

Transcript edited for clarity.

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