Comparing Elacestrant Vs Fulvestrant for ESR1-Mutated Breast Cancer

Claudine Isaacs, MD (Moderator)

Medical Director

Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research

Professor of Medicine and Oncology

Associate Director of Clinical Research and Leader, Clinical Breast Cancer Program

Lombardi Comprehensive Cancer Center at Georgetown University

Washington, DC

DISCUSSION QUESTIONS

• What do you see as the role of elacestrant (Orserdu) in your practice now that it has been approved? ​
• How do you envision the role of aromatase inhibitors (AIs) and fulvestrant (Faslodex) changing with this new approval?​
• What do you see as the pros and cons of elacestrant versus fulvestrant specifically for tumors that are estrogen receptor positive (ER+), HER2 0, with an ESR1 mutation?​

CLAUDINE ISAACS, MD: What do you think about the plusses and minuses of [elacestrant] versus fulvestrant? [If] you’re sitting across from your next patient where you're making your choice about a SERD [selective estrogen receptor degrader], how do you feel about this?

We all have patients where we think [about] how are we keeping on with these intramuscular injections and have been promised an oral SERD. If you had a patient and you're thinking about the pros and cons of elacestrant versus fulvestrant in a patient with an ESR1 mutation, where are you landing these days?

GEORGE KANNARKAT, MD: I think this is great; it's an option. What sometimes gets in the way is out-of-pocket cost to the patient. Some of the drugs get covered better when they're given in the office than when patients have to get these things through their mail order pharmacies.

Whatever the copay is, 20% of a large payment is still a [significant cost]. That's the only downside I see, and everything else displayed as far as the data are all encouraging, not a home run compared with fulvestrant, but a step in the right direction, taking a pill medication every day of the month versus a shot or 2 shots once a month.

I don't have any other qualms about prescribing oral elacestrant to any of the patients who we were previously giving fulvestrant. Mainly the cost, and I think we all have probably a patient that we're going to see in the next month where this is going to come up. We’ll see how that cost plays into it.

NINA BALANCHIVADZE, MD: I agree [concerning] the cost. I believe the cost of elacestrant [much higher than] for fulvestrant, so price will be one [factor], and that might help sway depending on the patient. How long they have been on prior therapy would be another [factor]. Overall, I'm looking forward to using it.

DISCUSSION QUESTION

• Please discuss your preferred subsequent-line sequencing strategy for ER+, HER2 0 metastatic breast cancer that is found to harbor an ESR1 mutation after adjuvant endocrine therapy (ET) therapy and a first-line CDK4/6i plus ET.​

ISAACS: [We are] asking a question about sequencing for a patient who developed metastatic disease after receiving adjuvant ET and a first-line CDK4/6 inhibitor plus ET. So, if they’ve had an AI within the past year, you're typically going to give the patient fulvestrant plus CDK4/6 inhibitor, if not AI plus CDK4/6 inhibitor.

The question is what you are doing second-, third-, fourth-line, and beyond, and the key things that drive you to make those recommendations. What are your second-line choices influenced by?

BALANCHIVADZE: [My choices are influenced by which] other mutations there are. PI3K, or if there are germline BRCA mutations, those are the main ones that drive my second-line [therapy], and then ESR1 as of now; so that's where my second line would fall on. If I don't have any of those mutations, I would think of everolimus [Afinitor] there.

In the third line I'd look at the HER2 status, [but if] it’s HER2 0, then beyond that I'd think about single-agent chemotherapy. Then after that, I start thinking about [sacituzumab govitecan (Trodelvy)] if I've had ET plus at least 2 lines of chemotherapy.

ISAACS: What if she doesn't have a PIK3CA mutation but the tumor has an ESR1 mutation in this setting, based on looking at all the data?

ARUN BHANDARI, MD: Yes, I would [use] elacestrant.

MAURA HAGAN, MD: Is the nausea [with elacestrant] something that goes away? Because at least…one-third of patients are going to get nauseated,¹ and I don't remember that many patients on fulvestrant ever coming in other than complaining about coming in every month to get 2 shots, talking about nausea. That's going to be a quality-of-life issue unless it subsides pretty quickly.

ISAACS: I haven’t seen the data presented on the duration [of this toxicity], but very few patients had dose reductions, and very few patients came off therapy due to toxicity, so presumably it either got better with time or [the investigators] figured out how to manage it. But those are important points.

DISCUSSION QUESTIONS

• Please consider a patient with ER+, HER2-0 metastatic breast cancer who experiences disease progression while on first-line ET plus CDK4/6i for de novo disease. Molecular panel testing via liquid biopsy is positive for an ESR1 mutation. How are you likely to sequence therapy for this patient?​

ISAACS: Are there any things here that we haven't touched on that influence your recommendation for second-line therapies?

BHANDARI: [There may be issues with] adherence to [an oral] therapy. Especially if there is a significant nausea, a patient may not take it, or they may take a lower dose.

ISAACS: If you have a patient who you worry might not be so adherent, are you likelier to have them to come into the office to get fulvestrant [as an injection as opposed to oral elacestrant]?

BHANDARI: Probably, yes. [I might] give it a trial run. If they're not taking it as they are supposed to, [I would] probably do fulvestrant.

HAGAN: We've all been horrified by the number of patients who don't manage to stay on their tamoxifen or their AI when you do the pill counts and follow-up on what they're going to the pharmacy for. It's [disappointing] to get the call from the insurance company that your patient hasn't gotten something filled for the last 3 months. At least with the fulvestrant, if they don't come in, you call them [and] you get them back in. This is their life [at stake].

_Reference:

_{1. Bidard FC, Kaklamani VG, Neven P, et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol. 2022;40(28):3246-3256. doi:10.1200/JCO.22.00338}