Oral elacestrant vs standard-of-care in estrogen receptor-positive, HER2-negative (ER+/HER2-) advanced or metastatic breast cancer (mBC) without detectable ESR1 mutation (EMERALD): Subgroup analysis by prior duration of CDK4/6i plus endocrine therapy (ET).

person Virginia G. Kaklamani UT Health San Antonio, San Antonio, TX info_outline Virginia G. Kaklamani, Francois Clement Bidard, Patrick Neven, Alberto J. Montero, Marie-Ange Mouret-Reynier, Joohyuk Sohn, Donatienne Taylor, Frederic Forget, Kathleen Kiernan Harnden, Hung T. Khong, Judit Kocsis, Florence Dalenc, Patrick Michael Dillon, Simon Waters, José A. García-Sáenz, Philippe Georges Aftimos, Javier Cortes, Simona Scartoni, Nassir Habboubi, Aditya Bardia

Authors person Virginia G. Kaklamani UT Health San Antonio, San Antonio, TX info_outline Virginia G. Kaklamani, Francois Clement Bidard, Patrick Neven, Alberto J. Montero, Marie-Ange Mouret-Reynier, Joohyuk Sohn, Donatienne Taylor, Frederic Forget, Kathleen Kiernan Harnden, Hung T. Khong, Judit Kocsis, Florence Dalenc, Patrick Michael Dillon, Simon Waters, José A. García-Sáenz, Philippe Georges Aftimos, Javier Cortes, Simona Scartoni, Nassir Habboubi, Aditya Bardia Organizations UT Health San Antonio, San Antonio, TX, Institut Curie, Paris and Saint Cloud, France, Universitaire Ziekenhuizen (UZ) - Leuven Cancer Institute, Leuven, Belgium, University Hospitals Seidman Cancer Center, Cleveland, OH, Jean Perrin Cancer Centre, Clermont-Ferrand, France, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, Université Catholique de Louvain, CHU UCL Namur – Site Sainte-Elisabeth, Namur, Belgium, Centre Hospitalier de l'Ardenne - Site de Libramont, Libramont-Chevigny, Belgium, Inova Schar Cancer Institute, Fairfax, VA, Moffitt Cancer Center, Tampa, FL, Bacs Kiskun Megyei Korhaz, Kecskemét, Hungary, Institut Claudius Regaud, Institut Universitaire du Cancer – Oncopole, Toulouse, France, University of Virginia, Charlottesville, VA, Velindre Cancer Centre, Cardiff, United Kingdom, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), Madrid, Spain, Medical Oncology Department, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium, Brussels, Belgium, International Breast Cancer Centre (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain, Menarini Group, Florence, Italy, Stemline Therapeutics/Menarini Group, New York, NY, Massachusetts General Hospital Cancer Center, Boston, MA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Stemline Therapeutics, Inc Background: The phase 3 EMERALD trial reported significantly prolonged progression-free survival (PFS) and a manageable safety profile with oral elacestrant (Ela) vs standard of care ET (SoC) in patients (pts) with ER+/HER2− mBC following progression on prior endocrine and CDK4/6i therapy. Duration of prior CDK4/6i was shown to be a potential predictor of efficacy in pts with ESR1 mutations ( ESR1 m) receiving elacestrant. Median PFS (mPFS) for pts with ESR1 m receiving <6 mos of prior CDK4/6i was 1.87 mos (Ela) vs 1.87 mos (SoC), compared with 4.14 mos (Ela) vs 1.87 mos (SoC) for pts receiving CDK4/6i ≥6 mos and 8.61 mos (Ela) vs 1.91 mos (SoC) for pts receiving ≥12 mos of prior CDK4/6i. Understanding the clinical activity of Elacestrant in ESR1 non-detected ( ESR1 nd) ER+/HER2- mBC is still needed. Preclinical ER+ PDX models suggest that elacestrant is equally active in ESR1 wild-type ( ESR1 wt) and ESR1 m. In the PDX model ST3932 ( ESR1 wt), derived from a pt treated with palbociclib plus aromatase inhibitor (AI) that was resistant to palbociclib in vivo, elacestrant demonstrated statistically significant single-agent antitumor activity (Patel, 2019). Methods: Pts with ER+/HER2- advanced or mBC who previously had 1-2 lines of ET, mandatory CDK4/6i, and ≤1 chemotherapy were randomized, 1:1 to receive oral elacestrant or SoC (investigator’s choice of AI or fulvestrant). An ad hoc subgroup analysis was performed on pts with ESR1 nd by prior duration of CDK4/6i plus ET (<6 mos, ≥6 mos, ≥12 mos) in the advanced or metastatic setting. Results: Among the 478 pts enrolled, 250 (n=124, Ela; n=126, SoC) did not have a detectable ESR1 m. Interestingly, in 41 pts with ESR1 nd (n=20, Ela; n=21, SoC) that rapidly progressed on prior CDK4/6i plus ET (<6 mos), treatment with elacestrant was associated with prolonged mPFS vs SoC (5.32 mos vs 1.87 mos, respectively) (HR=0.518 [95% CI 0.216-1.165]), compared with a mPFS of 1.91 mos (Ela) vs 1.97 mos (SoC) for pts who were on CDK4/6i for ≥6 mos (HR=0.911 [95% CI 0.640-1.298]) and 2.33 mos (Ela) vs 2.04 mos (SoC) for pts who were on CDK4/6i for ≥12 mos (HR=0.886 [95% CI 0.586 - 1.337]). In these 41 pts, mean time to chemotherapy was 137.7 days for elacestrant vs 75.5 days for SoC. Safety results were consistent with previously reported data. Specific pt characteristic information will be provided in the presentation. Conclusions: In this post-hoc analysis, oral elacestrant delayed disease progression and time to subsequent chemotherapy in pts who did not have a detectable ESR1 m and rapidly progressed within 6 months of CDK4/6i plus ET before study entry. Preclinical data support these findings. While caution needs to be exerted given small numbers, the results highlight the potential role of elacestrant in ESR1 wt tumors, and more research is warranted. Clinical trial information: NCT03778931.

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