Design: Phase 3, randomised, open-label
Population: 373 patients with ER+/HER2− advanced breast cancer after a CDK4/6 inhibitor
Primary outcome: Investigator-assessed progression-free survival (ESR1-mutated, then overall)
Effect: ESR1-mutated: 10.0 vs 5.5 months, HR 0.38 (0.27–0.54); overall HR 0.56

evERA was a phase 3, open-label trial in 373 patients with ER-positive, HER2-negative advanced breast cancer that had progressed after a CDK4/6 inhibitor plus endocrine therapy. Patients received oral giredestrant, a selective oestrogen receptor degrader, plus everolimus, or standard endocrine therapy (exemestane, fulvestrant or tamoxifen) plus everolimus.

In the 207 patients with ESR1-mutated tumours, median progression-free survival was 10.0 against 5.5 months (HR 0.38, 95% CI 0.27–0.54). Across all patients it was 8.8 against 5.5 months (HR 0.56, 0.44–0.71). Adverse events were similar in both arms, with stomatitis in nearly half.

The gain was concentrated in ESR1-mutated disease, which makes testing for that mutation at progression more relevant. Overall survival data are not yet reported.

ESR1 mutations arise under endocrine therapy and are usually tested on circulating tumour DNA at progression.
Stomatitis affected nearly half of patients on everolimus in both arms; preventive mouthwash is standard practice.
The benefit in tumours without ESR1 mutation is less certain from this report.
Progression-free survival is not overall survival; longer follow-up is awaited.

Why it matters

Second-line endocrine therapy is moving from one-size-fits-all to mutation-guided.

The statistics, in plain English

A hazard ratio of 0.38 means progression or death occurred at well under half the rate in the giredestrant group among ESR1-mutated tumours. The overall figure is diluted by patients without the mutation.