Balancing Efficacy and Toxicity of Oral SERDs in Breast Cancer

In patients with metastatic breast cancer (mBC) who progress after first-line treatment of CDK4/6 and aromatase inhibitors (AI), the landscape of treatment options has expanded. Selective estrogen receptor degraders (SERDs) offer a convenient oral treatment option, but physicians are split on their efficacy and toxicity in real-world practice.

In a virtual Case-Based Roundtable event moderated by Aditya Bardia, MD, MPH, professor in the Department of Medicine and director of Translational Research Integration at UCLA Health, participants discuss the clinical realities of oral SERDs, trial data vs practice, and future considerations with newer agents that may offer a better balance of efficacy and adverse effects (AEs).

Register today to join a Case-Based Roundtable near you.

CASE SUMMARY

• A 48-year-old woman has been receiving ribociclib (Kisqali) and AI for mBC (estrogen receptor-positive [ER+] 75%, progesterone receptor-negative, HER2 1+ by immunohistochemistry; BRCA1/2 wild type) with bone involvement
  • 20 months after starting ribociclib plus AI, asymptomatic disease progression if discovered on follow imaging (bone progression and 2 small lung lesions)
• ctDNA testing: ESR1 mutation and no other actionable alterations

DISCUSSION QUESTION

• Have you used an oral SERD for any of your patients with ESR1-mutated, ER+, HER2– mBC?

Birendra Kumar, MD: I have used elacestrant and, in general, the response is not long lasting. There are some [AEs] , including fatigue, pain, and some gastrointestinal effects, but they can be managed. But I’m not too impressed with the drug so far.

Nithya Palanisamy, MD: I would agree. I’ve used it in maybe 3 or 4 patients. I’ve been underwhelmed by the response. We can keep patients on it for maybe 4 to 5 months at best and maybe stabilize disease or slow progression during that time, but I wouldn’t say my patients have done well on it in terms of response.

Pamela Miel, MD: My patient was on it for 6 months, then she progressed and I put her on [alpelisib (Piqray)]. I think hypercholesterolemia was the main [AE] .

DISCUSSION QUESTIONS

1. Consider the EMBER-3 (NCT04975308) and EMERALD (NCT03778931) efficacy and safety data. What are your reactions?

Aditya Bardia, MD, MPH: Looking at the data, what stands out in terms of efficacy and safety and moving forward, what would be your practice in terms of using elacestrant and imlunestrant?

Kumar: I have not used imlunestrant, but if diarrhea is more common with imlunestrant, then that might become a problem, because that's one of the [AEs] that's annoying to the patients.

Elisa Bomgaars, MD: I think I'm more impressed with the EMERALD study [of elacestrant] because it had patients with poorer prognosis. The fact that they still showed a difference, it’s more impressive to me.¹

Melody Benjamin, MD: If you were combining abemaciclib and imlunestrant, I think the diarrhea would be potentially a problem, because it’s attractive to be able to use both of those, but then to be able to have so much more diarrhea, that’s the concern.

Bardia: That makes sense. What’s been your experience in terms of safety when a patient was on elacestrant?

Nithya Palanisamy, MD: The patients tolerated it quite well. I don't think we ran into any major [AEs] , but the data that you showed, I think the response rate seems to be similar.

Bardia: In terms of what was seen in the study, in clinical practice, has there been any difficulty with nausea?

Palanisamy: I think they did have some nausea, but it wasn’t anything major. I think it was manageable with ondansetron.

Bardia: In general, that's been our experience as well. It's not like T-DXd [trastuzumab deruxtecan; Enhertu] or [sacituzumab govitecan (Trodelvy)] nausea. It’s milder.

DISCUSSION QUESTIONS

• How do these data inform your second-line therapeutic selection for patients among those with ESR1-mutated, ER+, HER2-low mBC?
• Is there a clinical scenario or patient type where you would consider single-agent imlunestrant over single-agent elacestrant?

Miel: It might be the insurance that decides. In terms of [AEs] , if there's a patient who has a bad case of hypercholesterolemia, you might want to avoid elacestrant.

Bardia: Aboslutely. In [EMERALD], hypertriglyceridemia was seen.¹ And you’re right, institutional pathways or practice may dictate one over the other.

How are you deciding between single-agent vs combination therapy with abemaciclib, or even everolimus plus fulvestrant? Is it disease characteristics, bone metastases, visceral metastases, patient preference?

Vajeeha Tabassum, MD: I think a lot of it depends on all of the above factors that you just mentioned. And if it is someone with a low tumor burden, and the patient doesn't want too many [AEs] , then it's a shared decision making to put them on a single agent. I don't do that often, but it depends on the patient and the risks and benefits. I might be open to that idea, but a lot of it depends on multiple factors and a case-by-case basis

Miel: I agree. Less disease burden, you might choose single agent. Some patients really don't want to have to come in for injections.

DISCLOSURES: Bardia reported grants and personal fees from Novartis, Genentech, Merck, Pfizer, Menarini, AstraZeneca, Daiichi Sankyo, Alyssum, and Eli Lilly.

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 Oct 1;40(28):3246-3256. doi: 10.1200/JCO.22.00338. Epub 2022 May 18. Erratum in: J Clin Oncol. 2023 Aug 10;41(23):3962. doi: 10.1200/JCO.23.01239.