evERA: giredestrant plus everolimus nearly doubled progression-free survival in ESR1-mutated breast cancer

Design

Phase 3, open-label randomised trial, giredestrant plus everolimus vs endocrine therapy plus everolimus

Population

373 patients with ER-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor; 207 ESR1-mutated

Primary outcome

Investigator-assessed progression-free survival, ESR1-mutated then overall

Effect

ESR1-mutated: 10.0 vs 5.5 months, HR 0.38 (95% CI 0.27 to 0.54); overall: 8.8 vs 5.5 months, HR 0.56 (0.44 to 0.71)

evERA was a phase 3, open-label, randomised trial in 373 patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer that progressed after a CDK4/6 inhibitor plus endocrine therapy. They received giredestrant plus everolimus (183) or standard endocrine therapy (exemestane, fulvestrant or tamoxifen) plus everolimus (190). The primary end point, investigator-assessed progression-free survival, was tested first in ESR1-mutated tumours and then overall.

In 207 patients with ESR1-mutated tumours, median progression-free survival was 10.0 vs 5.5 months (HR 0.38, 95% CI 0.27 to 0.54; P<0.001). In the overall population it was 8.8 vs 5.5 months (HR 0.56, 0.44 to 0.71; P<0.001). Adverse events were similar (98.9% vs 96.8%), with stomatitis the most common (about 47 to 49% in both arms), followed by diarrhoea and anaemia.

The trial was open label, sponsor-funded, and measured progression-free survival by investigators. Overall survival is not reported in the abstract. Whether the regimen is available in your country is unknown here; giredestrant should be treated as investigational unless approved locally.

• Consider checking ESR1 status at progression on a CDK4/6 inhibitor plus endocrine therapy.
• The biggest gain was in ESR1-mutated disease (10.0 vs 5.5 months).
• Stomatitis affected about half of patients in both arms; plan mouth care.
• Overall survival data were not in the abstract, so weigh benefit against cost and access.
• Check regulatory status and access locally before discussing this regimen.

Why it matters

It gives a post-CDK4/6 setting a randomised comparison that favours an oral oestrogen-receptor degrader combination, especially where ESR1 is mutated.

Don't overread it

The result is progression-free survival in an open-label, sponsor-funded trial, and overall survival was not reported in the abstract.

The statistics, in plain English

A hazard ratio of 0.38 means about a 62% lower rate of progression or death at any time in the ESR1-mutated group. Progression-free survival is a surrogate for survival and quality of life, and investigator assessment in an open-label trial can bias towards the new drug.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.