Abstract PS7-07: Elacestrant plus abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC)

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Abstract Background: Endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i) is the primary first-line treatment for ER+/HER2- mBC; however, resistance eventually develops. In the EMERALD trial, single-agent elacestrant significantly prolonged progression-free survival (PFS) vs standard-of-care (SOC) ET with manageable safety in pts with ER+/HER2-, mBC previously treated with ET+CDK4/6i (ESR1-mut tumors: HR = 0.55; 95% CI, 0.39-0.77; P = 0.0005; all pts: HR = 0.70; 95% CI, 0.55-0.88; P = 0.0018). In those with prior ET+CDK4/6i ≥12 months and ESR1-mut tumors, median PFS with elacestrant was 8.6 vs 1.9 months with SOC ET. Combining elacestrant + abemaciclib (abema) may overcome additional resistance mechanisms, improve efficacy, and enable an all-oral treatment option that can replace fulvestrant-based combinations and delay chemotherapy or ADC-based regimens. Elacestrant + abemaciclib combination is being evaluated in the phase 1b/2 ELECTRA (NCT05386108) and ELEVATE (NCT05563220) trials. Here, we present a pooled analysis of efficacy and safety.Methods: Eligible pts were treated for ER+/HER2- mBC in ELECTRA and ELEVATE trials. Pts must have previously received ET in mBC, including ≥1 line of ET, CDK4/6 inhibitors, or chemotherapy (ELECTRA only). Safety was evaluated in all patients who received elacestrant + abemaciclib. The efficacy evaluable population included pts who had measurable disease (ie, ≥1 target lesion) at baseline and ≥1 post-baseline RECIST assessment.Results: As of July 2024, 55 pts have received elacestrant + abemaciclib, the majority with 1-2 lines of prior ET (91%), prior CDK4/6i (95%), and visceral metastases (66%); 25% received prior chemotherapy. The most common all-grade AEs (≥20%) were diarrhea (n=37, 67%; 2% Gr ≥3), nausea (n=34, 62%; 6% Gr ≥3), neutropenia (n=17, 31%; 27% Gr ≥3), vomiting (n=16, 29%; 2% Gr ≥3), fatigue (n=12, 22%; 2% Gr ≥3), anemia (n=11, 20%; 4% Gr ≥3), and decreased appetite (n=11, 20%; 0 Gr ≥3). No Grade 4 AEs were observed. In all efficacy-evaluable pts (n=27), mPFS was 8.6 mo. In the ESR1-mut population (n=11), mPFS was 8.7 mo. In ESR1-mut not detected (n=13), mPFS was 7.2 mo. In patients with only 1-2 lines of prior ET in mBC (n=23), mPFS was 8.7 mo. Median PFS according to dose level was 8.6 mo (elacestrant 258 mg QD + abema 100 mg BID, n=8), 7.5 mo (elacestrant 345 mg QD + abema 100 mg BID, n=7), and 8.7 mo (elacestrant 345 mg QD + abema 150 mg BID, n=12). Elacestrant 345 mg QD + abema 150 mg BID was determined as the recommended phase 2 dose (RP2D) for both ELECTRA and ELEVATE Phase 2 arms. Updated safety and efficacy will be reported.Conclusion: The RP2D dose combination of elacestrant 345 mg QD + abemaciclib 150 mg BID shows favorable efficacy with a manageable and predictable safety profile. Elacestrant has the potential to become the ET backbone for combination regimens. The Phase 2 portions of both studies are currently enrolling. Citation Format: Hope S. Rugo, Sara M. Tolaney, Nancy Chan, Erika Hamilton, Eva Ciruelos, Ji-Yeon Kim, Elena López-Miranda, Elia Seguí, Neelima Vidula, Joyce O’Shaughnessy, Giuseppe Curigliano, Javier Cortés, Alessandro di Sanzo, Paula Muñoz Romero, Bartomeu Piza Vallespir, Manuel Domínguez-Lizarbe, Kathy Puyana Theall, Alessandro Paoli, Monica Binaschi, Tomer Wasserman, Virginia Kaklamani. Elacestrant plus abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS7-07.

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