All-Oral Elacestrant Combos Offer “Tremendous” Benefits in Breast Cancer

Combining elacestrant (Orserdu) with other orally available targeted agents like abemaciclib (Verzenio) or everolimus (Afinitor) may offer a “tremendous number of benefits” compared with other modalities like chemotherapy and antibody drug conjugates in estrogen receptor (ER)–positive, HER2-negative breast cancer, according to Hope S. Rugo, MD.

In a conversation with CancerNetwork® at the 2025 San Antonio Breast Cancer Symposium (SABCS), Rugo discussed findings from the phase 1b/2 ELEVATE trial (NCT05563220), which demonstrated a clinically meaningful progression-free survival benefit with elacestrant plus abemaciclib or everolimus. Beyond these efficacy and safety findings, Rugo highlighted how the availability of an all-oral elacestrant-based regimen may offer a quality of life benefit compared with other standards of care.

According to Rugo, professor in the Department of Medical Oncology & Therapeutics Research, division chief of Breast Medical Oncology, and the Women’s Cancers Program Director at City of Hope, avoiding regularly scheduled intramuscular injections with other agents like fulvestrant (Faslodex) may provide a “big quality of life improvement” when using elacestrant-based regimens. Despite differences in toxicities like the risk of nausea and interstitial lung disease, she stated that these events are mostly avoidable, as dose reductions and toxicity management can be easily executed.

Transcript:

Generally, I would compare that all-oral regimen of elacestrant with a targeted agent to fulvestrant with a targeted agent, where you have to come in for 2 [intramuscular] injections every month, and in the first month, every 2 weeks. That’s a big quality of life improvement for patients if well-tolerated and, of course, with dose reductions as needed.

[However], I have to say we didn’t see much in the way of dose reductions in the phase 2 ELEVATE trial; this would represent a lot of freedom for patients in terms of scheduling and coming in compared with antibody drug conjugates and chemotherapy. Of course, there are big differences: the nausea, the risk of interstitial lung disease, hair loss, low blood counts; all these things are mostly avoided. Even when we do see nausea with these combinations, or diarrhea like with abemaciclib, we generally understand how to control it. We can dose reduce and manage this easily, so you avoid the need for [intravenous] access. There’s just a tremendous number of benefits for patients to be able to extend the period that they’re on oral therapies.

Reference

Rugo H, Tolaney S, Chan N, et al. Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study. Presented at: 2025 San Antonio Breast Conference Symposium; December 9-12, 2024; San Antonio, TX. Abstract RF7-01.