Duration of first-line CDK4/6 inhibitor therapy in patients with ER-positive/HER2-negative metastatic breast cancer is associated with duration of progression-free survival (PFS) of subsequent treatment with elacestrant, a selective estrogen receptor degrader (SERD), results from a post-hoc analysis of EMERALD showed.
Endocrine therapy plus CDK4/6 inhibitor is a standard first-line treatment for ER-positive/HER2-negative metastatic breast cancer.1 However, tumors eventually develop hormonal resistance. In current practice, sequential endocrine monotherapy or combination therapies are used in the second line. Sequential endocrine monotherapy is associated with low PFS after CDK4/6 inhibition; however, and combination therapy is associated with significant toxicity.2
Elacestrant is a next-generation selective estrogen receptor degrader (SERD), which has demonstrated a statistically significant improvement in PFS and manageable safety compared with single-agent endocrine therapy in the EMERALD trial.3 In this trial, prior CDK 4/ inhibitor usage was mandated. Prof. Virginia Kaklamani (University of Texas Health Sciences Center) presented results at the 2022 San Antonio Breast Cancer Symposium from a post-hoc analysis of EMERALD on the impact of duration of prior CDK4/6 inhibition on PFS.4
EMERALD enrolled 477 patients with advanced/metastatic ER-positive/HER2-negative breast cancer who progressed on CDK4/6 inhibition. Patients were randomized 1:1 to receive elacestrant or standard-of-care (SOC) endocrine therapy (fulvestrant, anastrozole, letrozole, or exemestane). The primary outcome was PFS.
Longer duration of CDK4/6 inhibition proved to be associated with longer PFS rates, both in the elacestrant arm and the SOC arm. However, this was more pronounced in the elacestrant arm resulting in a larger absolute benefit of elacestrant with longer duration of CDK4/6 inhibition. Benefit of elacestrant over SOC in PFS rate at 18 months was 13.21 months in patients with at least 6 months of CDK4/6 inhibition and 16.92 months in patients with at least 18 months of CDK4/6 inhibition. The benefit of elacestrant over SOC was even more pronounced in patients with ESR1-mutated tumors. Benefit of elacestrant over SOC in PFS rate at 18 months was 20.70 months in patients with at least 6 months of CDK4/6 inhibition and 30.68 months in patients with at least 18 months of CDK4/6 inhibition. No new safety signals were identified. Only 3.4% of patients discontinued elacestrant therapy due to any treatment-related adverse events.
Based on these results, Prof. Kaklamani concluded that “elacestrant can become an important oral endocrine monotherapy in second and third line as an alternative to combination therapies that are associated with challenging safety profiles.”
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