Evolving Landscape of HR+ Metastatic Breast Cancer Management


Closing out their review of treatment strategies for HR+ metastatic breast cancer, a panel of experts highlights ongoing investigations and future directions in care.


Jules Cohen, MD:Dr Slamon, this is a vague question, and I don’t know if it’s a good one, but why do you think some of these treatments are very biomarker dependent and some are not? Why do we need the PIK3CA mutation in order to use alpelisib, but we don’t need something similar for an AKT inhibitor or an mTOR inhibitor, which are both in the same pathway?

Dennis J. Slamon, MD, PhD: I think it’s incredibly exciting because we’re learning that there are targets where there’s a dependence on identifying if the target is activated or playing a role in the pathogenesis of the tumor. There are other targets where it is irrelevant. For example, for some of the surface membrane proteins that are targeted with ADCs [antibody-drug conjugates], it doesn’t matter whether it plays a role in the pathogenesis. If the antibody attaches to it, that complex is internalized, and it’s released inside, you have your activity. It’s going to be a learning process. There certainly won’t be a one-size-fits-all approach. Some things will require a biomarker, and others will not. It’s going to be on a case-by-case basis. It wasn’t a vague question at all. It’s a very relevant question and one that’s going to need to be addressed with data.

Jules Cohen, MD: Absolutely. Dr Mortimer, is there anything about ER [estrogen receptor]-positive HER2-negative metastatic breast cancer that we haven’t discussed that you would like to bring up?

Joanne Mortimer, MD, FACP, FASCO: My research involves functional imaging. Functional imaging of the estrogen receptor is an FDA-approved imaging agent. This is F18-labeled estradiol. I think the trade name is Cerianna. The use of FES PET [18F-fluoroestradiol positron emission tomography] as a predictor of endocrine sensitivity has certainly been shown in studies. I think one of the important data from the study isn’t just identifying who is responsive to endocrine therapy. Most of the data were derived pre-CDK4/6 inhibitors. We have a trial in Akron, Ohio, that has just completed accrual. We’ll find out if it predicts responsiveness to endocrine therapy with CDK4/6 inhibitors. What this PET study does, importantly, is tell you who doesn’t respond to endocrine therapy, which may be more important because you don’t waste the time of endocrine therapy on patients, and you can go right to nonendocrine interventions. I guess that would be my comment on what we haven’t talked about that has impact on hormone receptor-positive, HER2-negative breast cancer.

Jules Cohen, MD:Very nice. Dr Iyengar?

Neil M. Iyengar, MD: I think we’ve certainly hit all the high points. But I think that one of the really encouraging things is that with all of the agents we are seeing come through¾ in terms of new molecular therapies, new endocrine therapies, as well as the ADCs¾ we’re moving the needle in terms of time to chemotherapy. I think that’s particularly important for our younger patients with metastatic disease. We talked a bit about our premenopausal patients and the approach in those patients, but I think the field is moving toward sparing folks of chemotherapy, at least in earlier lines. The number of lines are increasing before we have to resort to chemotherapy. I find that to be very encouraging for our patients.

Jules Cohen, MD:Absolutely. Dr Slamon, is there anything else you’d like to add that we haven’t covered?

Dennis J. Slamon, MD: No, I think we’ve covered things fairly well. I think the excitement coming out of this year’s symposium is the spectrum of therapeutic options that are becoming available to us, that are effective, and that aren’t just statistically significantly different, but are clinically meaningful. You don’t need to be sitting in the first row to see the difference in the 2 Kaplan-Meier curve lines. The differences are getting to be pretty impressive when we know what therapeutics to use for what specific subpopulation, when it’s indicated. It’s very exciting, and it’s great news for patients with breast cancer.

Jules Cohen, MD:This is particularly important in this subgroup of ER-positive, HER2-negative patients, especially if they have bone-only disease or better prognostic features. It’s really become more of a chronic disease than a lethal or terminal disease. I think we can share that with our patients and give them a lot of hope in addition to getting them through treatment and keeping them on treatment for years at a time.

Dr Slamon, historically, when people use trastuzumab, we’ve continued trastuzumab or HER2-directed therapy for the entire course of their disease. Even if they progressed through first-line therapy, or second-line therapy, we may change the chemotherapy or hormonal therapy backbone but leave the trastuzumab on board. What about the CDK inhibitors in ER-positive disease? Are there any data that suggest we should keep the CDK inhibitor on board from first to second line and just change the endocrine partner?

Dennis J. Slamon, MD, PhD: The early bias, based on very few data, was if you’re resistant to one, you’re resistant to all. I think it’s a lot more nuanced than that, obviously, with the arrival of more data. I’m blanking on the name of the trial, but the trial that was presented….

Joanne Mortimer, MD, FACP, FASCO: MAINTAIN.

Dennis J. Slamon, MD, PhD: Yes, MAINTAIN. In terms of using ribociclib with different partners and maintaining the ribociclib, patients who had been on palbociclib and then progressed, or even patients who had been on ribociclib and progressed, it was surprising to see the response data and that there was an improvement. There clearly is a role. I don’t think it’s common. It’s not as common as switching the chemotherapy partner with trastuzumab, giving us efficacy, but it’s real and may be something worth trying. Now that we have a couple of different drugs that we can switch from/to that hit the same target, it’s a strategy worth thinking about.

Jules Cohen, MD: I’d like to thank our panel: Dr Iyengar, Dr Slamon, Dr Mortimer, and myself, Dr Jules Cohen. Thank you for joining us in this lively discussion on metastatic HR-positive breast cancer, brought to you by CancerNetwork®.

Thank you to our viewing audience. We hope you found this interactive discussion to be informative and beneficial to your clinical practice.

Transcript edited for clarity.

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