EMERALD: Prior CDK4/6 Inhibitor Therapy Tied to Results With Elacestrant
In the phase 3 EMERALD trial, a longer duration of prior treatment with a CDK4/6 inhibitor was associated with a greater PFS benefit from elacestrant in patients with ER-positive, HER2-negative, advanced breast cancer.4
The trial (ClinicalTrials.gov Identifier: NCT03778931) included 478 patients who were randomly assigned to receive elacestrant at 400 mg daily (n=239) or standard of care (SOC) ET, which was investigator’s choice of fulvestrant, anastrozole, letrozole, or exemestane (n=239). Patients were treated until disease progression or withdrawal.
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Previously published data suggested that elacestrant was associated with a 30% reduction in the risk of progression or death in all patients (hazard ratio, 0.70; 95% CI, 0.55-0.88; P =.002) and a 45% reduction in patients with ESR1-mutated tumors (hazard ratio, 0.55; 95% CI, 0.39-0.77; P =.0005), compared with standard ET.10
At SABCS 2022, Virginia Kaklamani, MD, of the University of Texas Health Sciences Center in San Antonio, presented a post hoc analysis investigating whether the duration of prior treatment with a CDK4/6 inhibitor influenced the PFS observed with elacestrant.4
The analysis showed that elacestrant improved PFS, but the magnitude of benefit was influenced by the duration of prior CDK4/6 inhibitor treatment. For patients who had received at least 6 months of prior CDK4/6 inhibitor treatment, the median PFS was 2.79 months with elacestrant and 1.91 months with SOC (hazard ratio, 0.688; 95% CI, 0.535-0.884).
For patients who received at least 12 months of prior CDK4/6 inhibitor treatment, the median PFS was 3.78 months with elacestrant and 1.91 months with SOC (hazard ratio, 0.613; 95% CI, 0.453-0.828). For patients who received at least 18 months of CDK4/6 inhibitor treatment, the median PFS was 5.45 months and 3.29 months, respectively (hazard ratio, 0.703; 95% CI, 0.482-1.019).
The PFS benefit with elacestrant was more pronounced among patients with ESR1 mutations, Dr Kaklamani noted. Among patients with ESR1 mutations who had received at least 6 months of prior CDK4/6 inhibitor treatment, the median PFS was 4.14 months with elacestrant and 1.87 months with SOC (hazard ratio, 0.517; 95% CI, 0.361-0.738).
Among patients with ESR1 mutations who had received at least 12 months of prior CDK4/6 inhibitor treatment, the median PFS was 8.61 months with elacestrant and 1.91 months with SOC (hazard ratio, 0.410; 95% CI, 0.262-0.634). For patents with at least 18 months of prior CDK4/6 inhibitor treatment, the median PFS was 8.61 months and 2.10 months, respectively (hazard ratio, 0.466; 95% CI, 0.270-0.791).
Updated safety data were consistent with previously reported results. Most of the AEs, including nausea, were grade 1 and 2. Treatment discontinuation due to an AE occurred in 3.4% of patients on elacestrant and 0.9% of those on SOC.
“Looking at the data, we, as clinicians, need to make a decision of whether we think the patient’s cancer is still endocrine sensitive, and, if it is, then elacestrant can be considered as one of the endocrine options,” Dr Kaklamani said in an interview. “Personally, I will use a cutoff of 12 months on prior CDK inhibitors and then consider elacestrant.”
“It is clear from the data that elacestrant is superior to standard-of-care endocrine therapy in ESR1-mutated tumors, but, in nonmutated tumors, elacestrant is still active and can be considered,” Dr Kaklamani said. “The trial wasn’t powered to look at that patient population, but based on the data, its activity is comparable with standard-of-care endocrine therapy.”
Disclosures: The monarchE trial was supported by Eli Lilly and Company. The RIGHT Choice trial was supported by Novartis Pharmaceuticals. The CAPItello-291 trial was supported by AstraZeneca. The EMERALD trial was supported by Stemline Therapeutics, Radius Health, and Menarini Group. Dr Goetz disclosed relationships with ARC Therapeutics, AstraZeneca, Biotheranostics, Biovica, Blueprint Medicines, Clinical Education Alliance, Curio Science, Eagle Pharmaceuticals, Eli Lilly, Pfizer, Research to Practice, Sanofi Genzyme, Sermonix, and Total Health Consulting. The study presenters and their colleagues declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of their disclosures.
References
1. Johnston S, Toi M, O’Shaughnessy J, et al. Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: Results from a pre-planned MonarchE overall survival interim analysis, including 4-year efficacy outcomes. Presented at SABCS 2022. December 6-10, 2022. Abstract GS1-09.
2. Lu Y-S, Mahidin EIBM, Azim H, et al. Primary results from the randomized Phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2− advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy. Presented at SABCS 2022. December 6-10, 2022. Abstract GS1-10.
3. Turner NC, Oliveira M, Howell S, et al. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the Phase III CAPItello-291 trial. Presented at SABCS 2022. December 6-10, 2022. Abstract GS3-04.
4. Bardia A, Bidard F-C, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: Updated results by duration of prior CDK4/6i in metastatic setting. Presented at SABCS 2022. December 6-10, 2022. Abstract GS3-01.
5. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987-3998. doi:10.1200/JCO.20.02514
6. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer; Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32(12):1571-1581. doi:10.1016/j.annonc.2021.09.015
7. Johnston SRD, Toi M, O’Shaughnessy J, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. Published online December 6, 2022. doi:https://doi.org/10.1016/S1470-2045(22)00694-5
8. First-line ribociclib plus endocrine therapy may be more effective than combination chemotherapy in patients with aggressive breast cancer. American Association for Cancer Research. News release. Published December 6, 2022. Accessed December 20, 2022.
9. Adding capivasertib to fulvestrant improves progression-free survival in patients with advanced hormone receptor-positive breast cancer. American Association for Cancer Research. News release. Published December 8, 2022. Accessed December 20, 2022.
10. 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;40(28):3246-3256. doi:10.1200/JCO.22.00338
