Drs Vidula and Langer review the role of oral selective estrogen receptor degraders in the treatment of ER+/HER2- metastatic breast cancer and which patient populations would benefit most from oral SERDs.
Ryan Haumschild, PharmD, MS, MBA: We’ve done a great overview of oral SERDs [selective estrogen receptor degraders] and some of the treatments that already exist in the space for our ER+ [estrogen receptor positive]/HER2- patients. Now let’s talk about the practice considerations for utilizing oral SERDs. We want to identify the appropriate patient populations for treatment with these oral SERDs, and how they fit into the treatment landscape. Dr [Neelima] Vidula, I’m going to come to you first. What is the role of oral SERDs in the treatment of ER+/HER2- metastatic breast cancer?
Neelima Vidula, MD: That’s a great question. When we think about the role of oral SERDs, it’s important to think about the broad road map for treating ER+/HER2- metastatic breast cancer. It’s a really great time for the field because we’ve seen the development of a number of different targeted therapies. In general, when we’re thinking about the management of ER+/HER2- advanced breast cancer, if a patient doesn’t have a visceral crisis—meaning impending organ dysfunction, which would necessitate chemotherapy—we are favoring starting with endocrine therapy or with targeted therapy combinations. When I think about a patient who doesn’t have any organ compromise and we’re seeing them in clinic, as a first-line agent, we would typically reach for a CDK [cyclin-dependent kinase] 4/6 inhibitor with endocrine therapy, either an aromatase inhibitor or fulvestrant depending on what they’ve received in the adjuvant setting and how far back that was. But that’s based on a number of different trials that have led to the approval of 3 different CDK inhibitors and notably a survival improvement with both abemaciclib and ribociclib. But after that first-line therapy, that’s where genomic testing becomes critical. It’s important to offer patients cell-free DNA testing and/or tumor tissue genotyping of a metastatic lesion to identify potentially actionable mutations because that’s really going to help guide what their next treatment options could be. In addition, it’s also important to offer genetic testing to patients because about 5% to 10% of patients may have BRCA1 or BRCA2 mutations, in which case they would be eligible for a PARP inhibitor at some point during their treatment course. We have 2 PARP inhibitors that are approved: talazoparib and olaparib. So those would be options for those patients who have germline BRCA1 or BRCA2 pathogenic mutations. But the genomic testing such as cell-free DNA or tumor tissue genotyping can help identify PIK3CA [phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha] mutations and ESR1 [estrogen receptor 1] mutations. And depending on what mutations you’re seeing, you can help tailor the next treatment for patients. For example, if a patient has a PIK3CA mutation, then you could consider alpelisib with fulvestrant, which is approved, based on the SOLAR-1 [NCT02437318] study, or put them on a trial with a different agent targeting PIK3CA. So that would be a great option for those patients. If a patient were found to have an ESR1 mutation, then they would potentially be able to consider elacestrant, which is approved, or a clinical trial with one of the many oral SERDs that Dr [Janice] Lu shared with us. So that’s how I would think about the overall road map for treating ER+/HER2- metastatic breast cancer. And certainly, all these targeted therapies help delay the onset of chemotherapy. But of course, we also have the approval of both sacituzumab and trastuzumab deruxtecan for HER2-low, ER+/HER2- advanced breast cancer as options when they do need to make that transition to chemotherapy in the future.
Ryan Haumschild, PharmD, MS, MBA: That was a great road map. I was actually writing everything down while you were talking because I think one of the main callouts that’s important is the overall survival for abemaciclib and ribociclib. I think [those are] important data that we’re seeing right now and how that drives therapy. But really where I want to transition is the importance of genomics and making sure in so many different solid tumor types like non–small cell lung cancer and colorectal, but breast, we really need to rely on having exactly really good precision medicine, and when we bring that in the frontline setting? Do we do it reflexively and make sure that we’re looking to those clinicians so we can optimally sequence these different therapies because more options are becoming available? Speaking of more options, we want to think about which patients are going to benefit the most from treatment with these oral SERDs for ER+/HER2- metastatic breast cancer. Dr [Lucy] Langer, I’d love to get your thoughts as a payer: Who is that patient population that would benefit the most, in your opinion?
Lucy R. Langer, MD, MSHS: I mean, clearly from the data that have been reviewed today, there’s a broad swath of patients [who] would be eligible. Those [who] have progressed on prior endocrine therapy, those [who] have progressed even on prior SERDs, and of course those with ESR1 mutation identified. So those are the 3 big buckets that I’m thinking about.
Ryan Haumschild, PharmD, MS, MBA: I think you nailed the buckets well and I think there’s going to be a lot of patients with the potential as we see more and more data and more SERDs that are coming down the pipeline [who] can really benefit from it. Maybe not in a second-line or third-line therapy, but even subsequent therapies, depending on [whether] they have genomic expression.
Transcript edited for clarity.