During a Case-Based Roundtable® event, Ruth M. O'Regan, MD, looks at options for a patients with hormone receptor–positive, HER2-negative breast cancer and an ESR1 mutation in the second article of a 2-part series.
Ruth O'Regan, MD (Moderator)
Professor
Chair
Charles Ayrault Dewey Professorship of Medicine
Department of Medicine (SMD)
University of Rochester Medical Center
Rochester, NY
CASE SUMMARY
Which therapeutic option would you choose?
RUTH M. O’REGAN, MD: Using fulvestrant plus a different CDK4/6 inhibitor would not be an unreasonable choice if the patient didn't have an ESR1 mutation. Fulvestrant alone isn’t a [definite] option for a patient like this. I probably wouldn't use exemestane plus everolimus [Afinitor] here because I don't think this patient has definitively endocrine-resistant disease. Likewise, I probably wouldn't give single-agent chemotherapy. So I would agree with the participants and give elacestrant [Orserdu].
TIFFANY A. TRAINA, MD: I absolutely agree. I think elacestrant would be a preferred option.1 But there are some other circumstances where somebody doesn't have access to elacestrant. The ESR1 mutation would drive me towards a selective estrogen receptor degrader over an aromatase inhibitor combination. So thinking about fulvestrant is also a reasonable option, but I think elacestrant [is a recommended] option.
O’REGAN: The patient received ribociclib in the first-line setting—if she got palbociclib [Ibrance], would you consider, if she didn't have any sort of mutation, fulvestrant plus ribociclib based on the MAINTAIN trial [NCT02632045]?
TRAINA: I think [we take into account] the MAINTAIN data.2 They are certainly compelling. I have done that very thing in patients who lack other targetable mutations, had a good run on first-line palbociclib, and just have a small amount of progression. We did see data that ribociclib plus fulvestrant was better than fulvestrant alone in that population. I would consider that, remembering that phase 2 hypothesis-generating study.
KAVITA B. KALRA, MD: If you have an ESR1 mutation as well as a PIK3CA mutation, what comes first? How do you deal with that?
O’REGAN: It's a very good question. It's a data-free zone, but I think given the toxicity profile, I probably would lean towards elacestrant.
TRAINA: I think this depends on the patient in front of you and the volume of their disease. Are they symptomatic, and are we feeling comfortable with single-agent endocrine therapy knowing that we still have the ability to target the PIK3CA pathway at the subsequent progression? I think in the absence of data, it's an art-of-medicine decision. I think there's a place for single-agent endocrine therapy, given the constellation of risk-benefit balance.
O’REGAN: When you look at SOLAR-1 [NCT02437318], the benefit with alpelisib [Piqray] was pretty significant.3 We just don't know the answer right now. And I think you're absolutely right, it depends on the patient.
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