Progression-Free Survival of Oral SERDs in Clinical Practice

EP: 1.Differences Between SERDs and Other Therapies

EP: 2.Efficacy of Oral SERDs in the EMERALD Trial

EP: 3.Safety Concerns Associated With Oral SERDs

EP: 4.Benefits of Using Oral SERDs

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EP: 5.Progression-Free Survival of Oral SERDs in Clinical Practice

EP: 6.Role of Oral SERDs in Treatment of ER+/HER2- in Metastatic Breast Cancer

EP: 7.ESR1 Mutation Confirmation With Oral SERDs

EP: 8.Coverage Considerations for Oral SERDs

EP: 9.Clinical Impact of Oral SERDs

EP: 10.Treatment Failure and Resistance Before Oral SERDs

EP: 11.Cardiovascular Risk and Menopausal Symptoms Associated With Oral SERDs

EP: 12.Monitoring and Managing Adverse Effects With Oral SERDs

EP: 13.Payer Perspectives on SERDs

EP: 14.Ensuring Access to Oral SERDs

EP: 15.How Patient Advocates Can Help the Newly Diagnosed

EP: 16.Empowering Patients With Metastatic Breast Cancer

EP: 17.Helping Patients With Metastatic Breast Cancer Enroll in Clinical Trials

EP: 18.Guiding Patients Through Complex Treatment Decisions

EP: 19.Patient Advocate's Role in Shared Decision Making

EP: 20.Helping Patients Overcome Health Disparities as a Patient Advocate

Ryan Haumschild, PharmD, MS, MBA: We talked about the improved benefit, and Dr [Janice] Lu, you gave a great overview of the EMERALD trial [NCT03778931] with a lot of the clinical end points. But I’d like to dive a little bit deeper with Dr [Neelima] Vidula: I’d love for you to really explain to our viewing audience how improved progression-free survival [PFS] is seen with oral SERDS [selective estrogen receptor degraders] and how that translates to clinical practice?

Neelima Vidula, MD: That’s a great question. In the EMERALD study, PFS led to the approval of elacestrant that compared elacestrant with standard-of-care endocrine therapies, which could include fulvestrant or an aromatase inhibitor. And in that study, they did note that the PFS improved 12 months in the arm that received elacestrant compared [with] standard-of-care hormone therapy. It was 22% vs 9% in the control arm. But that improvement was heightened in patients who had an ESR1 [estrogen receptor 1] mutation that was detected. And in that group that had ESR1 mutations, the 12-month PFS was 26% compared [with] 8% with standard-of-care therapies. They also went on to look at elacestrant vs fulvestrant. And again, in the arm that had an ESR1 mutation, there was an improvement in PFS with elacestrant compared [with] fulvestrant. So, the median PFS with elacestrant was 3.8 months compared [with] 1.9 months with fulvestrant. So I think that this is an opportunity for patients to receive an oral therapy, particularly if they have an ESR1 mutation, that may lead to an improvement in PFS compared [with] fulvestrant. That’s what the take-home message of this study is. But I will add that the other interesting feature of this study was that a portion of patients who were enrolled had received prior fulvestrant. So, it also suggests this could be an option for some patients who have received prior fulvestrant, have an ESR1 mutation, and could go on elacestrant. I think that’s appealing to patients because now you have another oral therapy that you could try that is like fulvestrant in many ways and it gives them another option. But I think in terms of clinical benefit, the way I counsel patients in my practice about this is that if they have an ESR1 mutation that’s found on cell-free DNA testing, or next-generation sequencing [NGS], then this is a really good option to consider because it can also delay the onset of chemotherapy use, which we know has more adverse effects.

Ryan Haumschild, PharmD, MS, MBA: You hit on a lot of really good comments; seeing elacestrant after fulvestrant is so innovative. Having additional therapies for these patients is what it’s really about. Especially being able to really translate the genomic ESR12 treatment…is another great comment. And thirdly, having it be a preferred agent over chemotherapy, I think all patients are welcome to new therapies like that. And as we evaluate it, obviously we look at the clinical trial data and analyze what the hazard ratio is and what patient population was a part of the inclusion criteria. But I know a lot of us clinicians as well as payers really look to the NCCN [National Comprehensive Cancer Network] guidelines. Dr Vidula, if you could, what do the most recent NCCN guidelines say about the utilization of these oral SERDS?

Neelima Vidula, MD: The NCCN guidelines have actually incorporated elacestrant into the guidelines for the treatment of ER+ [estrogen receptor positive] and HER2- breast cancer in the advanced setting. What we see in the NCCN guidelines is that elacestrant can be considered as an option in patients who have an ESR1 mutation found either in cell-free DNA or an NGS assay. A genomic assay, in other words. The NCCN guidelines also include other SERDs. So fulvestrant has been part of the NCCN guidelines for many years now, and that is seen in the NCCN guidelines as a combination therapy with CDK [cyclin-dependent kinases] 4/6 inhibitors in the first-line setting or the second-line setting depending on what the patient has previously received. There’s also the option of combining fulvestrant with alpelisib in patients who have a PIK3CA [phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha] mutation, also found either in cell-free DNA or a tumor tissue genotyping assay. So, we’re seeing these SERDs have now become part of the guidelines in these various ways.

Ryan Haumschild, PharmD, MS, MBA: That’s exactly what I was going to highlight, and you have said it well; it’s great to see the compendium of NCCN really take up these oral SERDs and evaluate the treatment and give that recommendation. I think the great thing about that as well is it translates to a lot to our payer guidelines and reimbursements when we see the NCCN go ahead and start including these. Then we know we’re going to have payer coverage and create more equitable access for a lot of our patients.

We’ve talked about elacestrant and I think it’s exciting to talk about that one, but it sounds like the pipeline is going to be exciting with many more oral SERDs to come. I think that’s important for us to keep an eye on. Dr Lu, I know you’re familiar with this space. When you think about the investigational oral SERDs that are in the pipeline, which ones are coming and how do they differ from the ones that are currently approved?

Janice Lu, MD: That’s a great question. We have 5 [SERDs] on the market with elacestrant being the only [that is] FDA approved. There are 4 more in development at this point. One of them is camizestrant. Camizestrant was impressive in the SERENA-2 [NCT04214288] study, which showed improved PFS in comparison [with] fulvestrant. So now they have SERENA-4 [NCT04711252] and SERENA-6 [NCT04964934] in combination with CDK4/6 inhibitors to evaluate the benefit of the combination compared to the standard of care. As well as if adverse effects come with paretic cardiovascular or ocular toxicity and if it seems manageable, we are looking forward to the data for SERENA-4 and SERENA-6 at this point. And then there are 3 more. One is the EMBER [NCT04188548] study. This is imlunestrant, so that’s another study being conducted. That’s a large study with 800 patients in a phase 3 study. So, it’s ongoing. We are looking forward to the data and then there are 2 more. One is based on the AMEERA-5 [NCT04478266] trial; that’s amcenestrant and the other one is giredestrant. These 2 studies so far are from a small phase 2 study, which did not meet the end point, but we’re looking forward to new studies, including this one for the adjuvant study as well. So, I think it’s exciting. One is working with elacestrant and 4 more are in the pipeline now for the landscape at this point.

Ryan Haumschild, PharmD, MS, MBA: It’s a great overview and it’s an exciting time for our patients and providers and really a welcomed opportunity to add more therapeutics into the space.

Transcript edited for clarity.