OBJECTIVES: Patients with ER+/HER2- advanced/mBC harboring ESR1 mutations face a significantly shortened disease progression. Elacestrant, a novel therapeutic option, is the first drug addressing the unmet medical need in patients with ESR1-mut tumors. This analysis was conducted to inform the UK cost-utility analysis and aims to compare the effectiveness of elacestrant versus everolimus + exemestane in a patient population with prior endocrine therapy (ET) + CDK4/6 inhibitor ≥12 months, leveraging RWD and clinical trial data while adjusting for differences in patient characteristics.

METHODS: Among patients who received everolimus + exemestane, aggregated baseline characteristics and information on disease progression and survival were extracted from Flatiron Health-Foundation-Medicine clinico-genomic database (CGDB) and compared with elacestrant patient-level data from the EMERALD study. The treatment comparison performed used the Matching-Adjusted Indirect Comparison (MAIC) method, accounting for differences in relevant patient characteristics, including age, number of prior lines of ET (1/2), and prior chemotherapy (yes/no). After matching, median overall survival (mOS), median progression-free survival (mPFS), and associated hazard ratios (HR) were estimated.

RESULTS: The analysis included 32 everolimus + exemestane “RWD” patients and 78 elacestrant EMERALD patients with prior ET+CDK4/6 ≥12 months. After matching, the effective sample size of elacestrant was reweighted to 66.5 (85.3%) patients. The mPFS and mOS were 4.57 and 17.97 months for everolimus + exemestane, and 8.61 and 27.73 months for elacestrant, respectively. After matching, the estimated mPFS and mOS for elacestrant were 7.39 and 27.73 months, respectively. The matched (MAIC) mPFS showed a HR of 0.59, 95% CI [0.36, 0.96], and mOS HR=0.64 [0.35, 1.16] for elacestrant versus everolimus + exemestane.

CONCLUSIONS: Our findings indicate that in patients with ER+/HER2- ESR1-mutated mBC who received prior ET+CDK4/6i ≥12 months, treatment with elacestrant is associated with a significant 41% reduction in the risk of progression or death compared to everolimus + exemestane.