Efficacy of Oral SERDs in the EMERALD Trial


Dr Lu reviews the efficacy of oral selective estrogen receptor degraders (SERDs) compared to other therapies for ER+/HER2– metastatic breast cancer.

Ryan Haumschild, PharmD, MS, MBA: When we talk about the efficacy of SERDs [selective estrogen receptor degraders], I think you did a great job talking about where they fit in within the treatment pathway. But I’d love to hear Dr Lu speak a little bit more about the efficacy of oral SERDs and maybe even reference some of the end points we saw in the EMERALD trial comparing that to other therapies. How do SERDs compare to your endocrine-based therapies or your CDK [cyclin-dependent kinases] 4/6 therapies in this ER [estrogen receptor] positive HER2 [human epidermal growth factor receptor 2] negative patient population?

Janice Lu, MD: That’s a great question. The oral SERD elacestrant is the only FDA-approved drug as of January of this year. So, we have 1 more option for patients. We were so delighted in the community for our patients, and for physicians to treat patients. Oral SERD elacestrant was [studied in] in the [phase 3] EMERALD trial [NCT03778931], with 477 patients randomly assigned 1-to-1 to elacestrant vs physician’s choice, including fulvestrant or AI [aromatase inhibitor], 1 of the 3 AIs. And then in the study for patients who got 12 months of treatment with CDK4/6 inhibitor, it was quite impressive. The patient got duration response and also progression-free survival [PFS] of 8.6 months who were treated with elacestrant vs physician’s choice with fulvestrant or AIs. That was only 1.9 months. Endocrine therapy and then sensitivity based on CDK4/6 inhibitor duration response is the surrogate marker. A couple of patients got a response of about 6-plus months. Then you may think about patients having some kind of resistance to endocrine therapy with CDK. Even oral SERD with elacestrant, they have 4.6 months of duration vs 4.1 months of duration response PFS vs physician’s choice of 1.9 months. The duration of treatment was at 12 months 41% of patients, up to 40% plus of patients, still stayed on elacestrant vs a significantly less percentage of patients stayed on AI vs fulvestrant. So those are the results from the EMERALD trial, which got FDA approval, and we use it quite frequently in clinics to benefit our patients at this point.

Ryan Haumschild, PharmD, MS, MBA: Great overview. I think one of the biggest things I take away is it’s not just the clinical improvement, but it’s a statistical improvement. I think having something post first- and second-line therapy, especially in this patient population, is going to be welcomed. And the more we can create those better PFS curves, I think that’s ultimately the goal. Another question that’s going to come up, and I know this comes up frequently in clinic or even in some patients who might have had another family member or someone else who has been ER-positive/HER2-negative, they’ll ask, how do oral SERDs compare with chemotherapy? If you have patients in this population traditionally treated with chemotherapy, how do oral SERDs compare to those end points?

Janice Lu, MD: That’s a great question. We don’t have to talk about the toxicity of chemotherapy, and the duration response is not optimal for patients with endocrine-sensitive disease. With endocrine-sensitive disease, endocrine therapies were CDK, AI, and fulvestrant in the past; now, oral SERD is the key point and we have other options like an Aromasin [exemestane] combination. I think we focus on endocrine therapy instead of chemotherapy. Chemotherapy’s duration response is quite often limited to months. We talk about 2 to 3 months, 4, 5, or 6 months will be very optimal already for that kind of duration vs elacestrant in the EMERALD trial, in comparison with the physician’s choice with AI fulvestrant was 8.6 months PFS. So I think that was quite impressive.

Ryan Haumschild, PharmD, MS, MBA: Impressive, indeed. When you think about some of the adverse effects of chemotherapy and the abandonment rates and the toxicity management, that is important and plays a strong role. But I think when you can offer something different from chemotherapy, it’s always welcomed. As we talk about things that are different from chemotherapy, we know a lot of these patients have been exposed to prior CDK4/6 use. We know at ASCO [the American Society of Clinical Oncology annual meeting], there is a lot of innovative data even from the San Antonio Breast [Cancer Symposium], and we’re always looking at how to best sequence medications, what does post CDK4/6 treatment really look like? When we think about that in the context of SERDs, and you hit on this a little bit before, can you discuss the data of oral SERDs in patients with prior CDK4/6 use for us once more?

Janice Lu, MD: Sure. For elacestrant, in the EMERALD trial, all patients were supposed to get CDK4/6 inhibitors. That was one of the requirements and eligibility. The patient surrogate marker is how long the patient got a response on the CDK4/6 inhibitor, and 12 months is something ideal. And most patients have a much longer duration response on CDK4/6 inhibitors. So if you take a look for 12 months, we have 8.6 months of PFS for patients with good response to CDK4/6 inhibitor vs physician’s choice was 1.9 months only. So that’s the data I want to stress one more time.

Ryan Haumschild, PharmD, MS, MBA: I’m glad you did, and I appreciate you reviewing the EMERALD trial and the data around SERDs because I think it’s good for us to understand how this therapy fits into the natural treatment course. What about CDK4/6-exposed patients? And I think ultimately we want to be able to enable our providers and key decision makers to make the best decisions for our patients, really improving their quality of life and obviously their overall survival.

Janice Lu, MD: Absolutely. One more point I wanted to add.

Ryan Haumschild, PharmD, MS, MBA: Yes.

Janice Lu, MD: You asked me about chemotherapy. In fact, people think if the patients have visceral disease, chemotherapy may be more effective. However, in the EMERALD trial, 70% of patients got visceral disease and 80% of patients got bone disease. The response was equally effective for patients with visceral disease. We shouldn’t limit physicians and patients from getting benefits from an oral SERD.

Ryan Haumschild, PharmD, MS, MBA: Great differentiator.

Transcript edited for clarity.

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