During a Targeted Oncology™ Case-Based Roundtable™ event, Claudine Isaacs, MD, discussed with participants their reactions to the data from the phase 3 EMERALD study of elacestrant for patients with metastatic ER+ breast cancer.
CLAUDINE ISAACS, MD: [To give a] summary of what we know about elacestrant and where we are with it, it’s an oral selective estrogen receptor degrader, and it's approved in postmenopausal patients who have ESR mutations and have disease progression after at least 1 line of prior endocrine therapy.1
The tablet dosing is interesting, [using] 345 mg and 86 mg tablets, and it's recommended to take it with food.2 Then [when using] the dose reductions, you start to [use] those 86 mg tablets if you have to go down a dose level. So, you go down to 258 mg and then to 172 mg. The reductions are only recommended for grade 3 and above toxicity. For grade 1, you keep going. For grade 2, you consider interruption [until] recovery of less than or equal to grade 1, and resume at the same dose. Once you start to get to higher grades, that's where you wait for recovery and you resume at the next lowest dose level, or if you have grade 4 and it's not tolerable, permanently discontinue.
HARISH MADALA, MD: In terms of efficacy, it's…not a home run. It's slightly more efficacious, but with the relatively safer tolerability. I think it's a great option, keeping in mind other options we have available. Patients would definitely appreciate a drug like this even if it [only] gives them…a minor benefit in terms of efficacy. [It does not have] an amazing response in terms of survival data, but it's a decent option.
ARUN BHANDARI, MD: Dr Isaacs, how bad were the visceral metastases? Two-thirds of patients have visceral metastases. Were there a lot [of patients in the trial who started with this]? Liver function tests [LFTs], etc—[was it a] significant issue?
ISAACS: I don't think there were eligibility criteria that would have excluded patients, but I don't know how high the LFTs were allowed to go. I'm sure that…these were not patients who were in visceral crisis.
BHANDARI: You mentioned the dose. It's very unique. Why didn't they keep it rounded to the nearest number? Was there any real difference for 4-mg [dosing]?
ISAACS: I do not know the answer to that. This is a relatively new drug for me too. It was approved and available for us [several months ago], so I have not had a lot of experience with it. It does seem like a strange dose to have chosen, but presumably there's some rationale behind it.
How do you feel it compares if you're making a decision? In this setting, if you had a patient who didn't have a PIK3CA mutation, what were you doing in December 2022 in terms of the next line of therapy after they progressed after their first-line CDK4/6 inhibitor and an AI [aromatase inhibitor]?
MADALA: We were using fulvestrant [Falsodex] if that wasn't used in the first line, especially for minor progression and for patients with a decent progression-free survival in the first line, an AI and CDK4/6 inhibitor. [If] there was a little bit more rapid progression and no actionable mutations, I was going to chemotherapy. The other option was everolimus [Afinitor] and exemestane [Aromasin]. It was reasonably well tolerated. But that's why I think [elacestrant] is a pretty good option.
BHANDARI: I echo [this point].
ISAACS: How do you think it compares, if you had to choose between this and everolimus and exemestane?
MADALA: For ESR1 mutations, [elacestrant] would be my choice. For lack of ESR mutations, I probably would still offer this, but I think everolimus is a reasonable option. It probably will be the next go-to. I don't know how efficacious [everolimus would be], but I would probably use [elacestrant].
ISAACS: Would you use prophylactic antiemetics in your patients if you're giving elacestrant based on the safety data?3
AMI CHITALIA, MD: I would probably use it prophylactically. I would stress to the patient to let us know if they're developing [nausea and vomiting], because there are adverse events [AEs] to [antiemetics] as well. But just as I'd push on the diarrhea with abemaciclib [Verzenio], I would push on this a little bit more and make sure that they let us know.
But generally, though this is a new drug, I feel fairly comfortable with it. I haven't personally had very good cases of efficacy for everolimus and exemestane. I've had a couple cases of pneumonitis with everolimus. I would be more apt to use this drug and be comfortable with it.
RAJ MANCHANDANI, MD: If we use fulvestrant after CDK4 inhibitor for [patients with an] ESR mutation, then we don't have any medication after that. Everolimus/exemestane, especially the everolimus part, is not easy to tolerate. Patients get a lot of symptoms with the hypoglycemia, neutropenia, pneumonitis. In those instances, looking at those AEs, this is a reasonable option with the modest efficacy and a tolerable AE profile. I would definitely consider using it after using fulvestrant.
1. 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
2. Orserdu. Prescribing information. Stemline Therapeutics, Inc; 2023. Accessed April 20, 2023. https://bit.ly/3ozccwv
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