Patients with hormone receptor (HR) positive metastatic breast cancer who acquired ESR1 mutations during prior aromatase inhibitor therapy had worse survival when treated with the aromatase inhibitor exemestane compared with fulvestrant, a combined analysis of the phase 3 SoFEA and EFECT trials found. The results were recently reported in Clinical Cancer Research.
The EFECT (ClinicalTrials.gov Identifier: NCT00065325) and SoFEA (ClinicalTrials.gov Identifier: NCT00253422) trials included patients with HR-positive metastatic breast cancer who had disease progression during nonsteroidal aromatase inhibitor therapy and randomly assigned them to receive fulvestrant 250 mg or exemestane.
The combined analysis included serum samples collected at baseline from 227 patients in EFECT and plasma samples collected at baseline from 161 patients in SoFEA. Using digital PCR, 383 samples were analyzed for ESR1 mutations, and 30% of samples were found to have ESR1 mutations.
Patients with ESR1 mutations had 1.5-month shorter progression-free survival (PFS) when treated with exemestane compared with fulvestrant (2.4 vs 3.9 months; hazard ratio [HR], 0.59; 95% CI, 0.39-0.89; P =.01). No difference in PFS was seen between exemestane and fulvestrant treatment groups for patients without ESR1 mutations (4.8 vs 4.1 months; HR, 1.05; 95% CI, 0.81-1.37; P =.69).
A restricted mean survival analysis showed a worse 1-year overall survival (OS) rate for patients with ESR1 mutations who received exemestane compared with fulvestrant (62% vs 80%; P =.04). No difference in 1-year OS rate was seen between exemestane and fulvestrant treatment groups for patients without ESR1 mutations (79% vs 81%; P =.69).
“We demonstrate that the detection of ESR1 mutations in baseline metastatic breast cancer circulating tumor DNA analysis predicts lack of benefit from subsequent aromatase inhibitor therapy,” the study authors concluded.
Turner NC, Swift C, Kilburn LS, et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor positive breast cancer: A combined analysis of the phase III SoFEA and EFECT trial [published online June 16, 2020]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-20-0224