Impressions of Elacestrant’s Efficacy in ER+, HER2- Breast Cancer

Mark Pegram, MD

Suzy Yuan-Huey Hung Endowed Professor of Medical Oncology

Stanford University School of Medicine

Associate Director of Clinical Research

Stanford Comprehensive Cancer Institute

Stanford, CA

DISCUSSION QUESTION

• What are the practical considerations for use of elacestrant (Orserdu) in patients with estrogen receptor (ER)-positive, HER2-negative breast cancer?

MARK PEGRAM, MD: The label indication is for postmenopausal ER-positive), HER2-negative, ESR1-mutated advanced or metastatic breast cancers and progression after 1 line or more of endocrine therapy.¹ The tablet size is…345 mg for the large tablet. If you have to do a dose reduction, you do so by using the 86-mg tablets. The first dose reduction is 3 of the 86-mg tablets. The second dose reduction is 2 of the 86-mg tablets. It’s taken once a day with food preferentially.¹

There are some other issues I want to talk about…and those are drug interactions. You have to be mindful of strong and moderate CYP3A4 inducers and inhibitors and avoid concomitant use of those agents with elacestrant. Please use the drug-drug interaction tables you can find online when you’re prescribing this drug, populate the patient’s other comedications, and make sure the pharmacist is happy with all the concomitant medications you’ve been using with elacestrant. Elacestrant is a PGP (P-glycoprotein) inhibitor, so be careful with the PGP substrate drugs. Also, you have to watch out for BCRP (breast cancer resistance protein) substrates with elacestrant as well.

The dose modification guidelines are…in the package insert. Consider interruption when you have grade 2 adverse events [AEs] or greater [until they are] less than or equal to grade 1. For grade 2 AEs, you can resume at the same dose level. For grade 3 and above, you [should] reduce by 1 dose level. If you get the same higher-grade toxicities on rechallenge, then you may need to dose reduce twice, or for grade 4 AEs you may need to permanently discontinue elacestrant if you’re having intolerant AEs that you can’t accommodate.

PREETI CHAUDHARY, MD: What about premenopausal women? Do you use it [in these patients]?

PEGRAM: Postmenopausal women or adult men is the exact label language. I suppose you could render a premenopausal patient physiologically postmenopausal with an LHRH (luteinizing hormone-releasing hormone) agonist like we do for other drugs like aromatase inhibitor [AI]?

SWARNA CHANDURI, MD: [These patients] are already on AI. We presume that we are prescribing only for postmenopausal patients.

PEGRAM: That’s true, yes. If you go by the label, you may get insurance kickback for premenopausal patients.

DISCUSSION QUESTION

• What are your reactions to the data from the EMERALD trial (NCT03778931)?

PEGRAM: What are your reactions to the efficacy data? Are you convinced that [approval for] the ESR1-mutated subgroup was the right decision by the FDA?

KELLY E. MCCANN, MD: I was disappointed that it was only the ESR1 subgroup.² I was hoping for an oral SERD [selective estrogen receptor degrader] that would replace the…shot that all the patients hate and then they could be moved into that adjuvant setting. That would be nice.

PEGRAM: They compared it with the fulvestrant [Faslodex] arm. It’s at least as good as fulvestrant.³ So, in the adjuvant setting, there may still be hope, in my opinion, for wild-type and ESR1-mutant patients. Because if oral SERDs as a class are as good as fulvestrant and if fulvestrant is better than AIs and better than [tamoxifen], which it is in the metastatic setting, then we might see a new oral SERD drug class in the adjuvant setting even for ESR1 wild-type patients in the future, theoretically. But we’ll have to do the trials.

What are your reactions to the safety data? What about the gastrointestinal toxicity, is anybody put off by that? Taking the drug with food ameliorates the drug toxicity, to some extent. But what do you think about comedication with an antiemetic, would you consider doing that if need be? Does that change your perception…of the use of the drug?

LUKE CHEN, MD: I don’t think it will deter me from using it. I haven’t used it, so I’m not sure what the AEs are. But looking at the data, it looks manageable. Nothing would scare me away from using it.

PEGRAM: Yes, it was such a low dose modification rate of only 3% and a low drug discontinuation rate. It would appear that the EMERALD population were well suited with the prescribing information recommendations, which I think is [why] you can start just with food, and then if you need to add an antiemetic, you can. You’re all used to dealing with musculoskeletal pain with AIs, so that’s no stranger to endocrine therapy.

_REFERENCES:

_{1. Orserdu. Prescribing information. Stemline Therapeutics, Inc; 2023. Accessed June 7, 2023. https://bit.ly/3ozccwv}

_{2. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. FDA. January 27, 2023. Accessed April 20, 2023. https://bit.ly/3Lib3m2}

_{3. 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}