Looking Towards The Future of HR+/HER2- Breast Cancer


The expert panel discusses ongoing research and offers closing thoughts on the future of HR+/HER2- breast cancer treatment.


Komal Jhaveri, MD, FACP: Any other exciting medications that we didn’t talk about? Maybe an exciting endocrine drug that you think we should probably know about or look out for [in] the future?

Timothy Pluard, MD: I think just the ones that we have we’re still awaiting the SERD [selective estrogen receptor degrader] to emerge. Some have fallen by the wayside, but we still need to get 1 across the finish line in addition to elacestrant [Orserdu]. We have multiple options: giredestrant, camizestrant, or lasofoxifene. A number of opportunities still to come.

Komal Jhaveri, MD, FACP: There are many, many novel endocrine therapies. Aditya, any excitement about which agent might make the finish line? I know it’s forecasting or prognosticating, but there seems to be like a breadth of these options that might be potentially available to our patients. How are you thinking about them? Do you think one might be better suited? Do you see or envision a scenario where maybe 1 drug might be even better for a mutation-specific? Even with ESR1 [estrogen receptor 1] mutations, do you think this particular option could be relevant for a Y537S mutation? Do you envision something like this, or do you just think that we will have many options and we might have to figure out how to sequence them?

Aditya Bardia, MD, MPH: We’ll likely have more than 1 option. Not just oral SERDs, there’s also interest in PROTACs [proteolysis targeting chimeras] like ARV-471. There’ll be multiple ways of targeting ER, which is good. In terms of Y537S, there does appear to be a difference. We know Y537S mutant tumors are more resistant to fulvestrant [Faslodex], but what’s the impact of different types of surge of an ARV-471? [We] will need data and maybe that would guide the use of these agents. The other thing that would guide the use of these agents is going to be the toxicity profile because it’s not identical. Some drugs cause diarrhea, [while] some cause bradycardia. I think that would factor into the decision-making as well.

Gregory Vidal, MD, PhD: And the ophthalmic toxicities too, which are also different between those drugs.

Komal Jhaveri, MD, FACP: Right. I think it’s very interesting that we have cardio toxicities and ophthalmologic toxicities that we have to keep a watch out for. Luckily, they’re low grade. What is not settling is that we don’t understand why does it happen, what is the mechanism behind them? Thankfully, they are low grade and time will tell how we will figure out utilizing these breadth of patients and hopefully many will reach the finish line and will again, have a good problem to solve for our patients and clinic as to which option to consider and why. I think I’d really like to thank all of you for this rich and informative discussion. I think before we can conclude, I’d really like to get some final thoughts from each one of you. Maybe, Tim, we can start off with you.

Timothy Pluard, MD: I would say that we are currently suffering from an embarrassment of riches in terms of the endocrine arena, and there’s going to be a lot of work to sort out what the best strategies are moving forward. But it’s a good place to be.

Komal Jhaveri, MD, FACP: Thank you. VK?

VK Gadi, MD, PhD: Yeah. I’m going to just to add to that exact statement and that exact sentiment. We have a lot of new agents. We have a lot of new biomarkers mixing them all up together and hoping for the dust to settle to figure out how this will look. We are fortunate in breast cancer to have strong guideline committees and, hopefully, they will make it easy for all of us to understand what’s the flow, what’s the pathway, [and] when do we order this test, when we do that? But as the data comes in, those pathways are just getting constructed right now. But it’s going to be transformative in the next few years for sure.

Komal Jhaveri, MD, FACP: Greg?

Gregory Vidal, MD, PhD: Yes. I agree with everything that was said. I will also add with all this new drug, there’s a cost that is going to be exorbitant. We have new drugs that are tripling the cost of what we expected and then when you do combination, those things we have to think about. I want to talk more about the fact that with all these new drugs, we’re going to need more biomarkers and with those biomarkers, we’re going to need more testing and more NGS [next-generation sequencing] testing, and then figuring out and educating physicians on when it’s appropriate to test and that we need to test because we still are not getting to the level of testing that we need to do. A lot to come.

Aditya Bardia, MD, MPH: I fully agree. Besides endocrine therapy, [there are] a lot of ADC [antibody-drug conjugate] options as well. We likely [are] going to see more and more agents and we might have to revisit our strategy in terms of just relying on randomized clinical trials because it’s just impossible to get the answer from a randomized trial. It might take 3 to 5 years, but then the feed advances and the control arm is not a relevant control arm. We’ll also have to rely on real-world data or other data sets to address some of the data gaps.

Komal Jhaveri, MD, FACP: I think [these are] such excellent points. One other thing that I would add is that we are utilizing CDK4/6 inhibitors in the early-stage setting. We have them in the first-line setting. When patients start progressing in our early stage on a CDK4/6 inhibitor, how do we tackle that in the metastatic setting? We spoke about ADC. Should we think about ADCs in that regard? Should we be thinking about PI3K [phosphoinositide 3-kinase] mutations in that regard? Should a triplet strategy make sense? Should ADC make sense? So we’ve really come a long way. There’s a lot more work to do, whether it’s biomarkers, whether it’s patient education, [or] whether it’s toxicity management. I’d really like to thank you again and to our viewing audience. We really hope you found this OncLive® Peer Exchange discussion to be useful and informative. Thank you.

Transcript edited for clarity.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

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