Objective:

To compare giredestrant plus everolimus with standard endocrine therapy plus everolimus in patients with ER-positive, HER2-negative advanced breast cancer, assessing progression-free survival (PFS) in the overall population and in patients with ESR1 mutations.

Approach:

• Study design: Global, randomized, open-label phase 3 evERA study.
• Participants and treatment: A total of 373 patients received either oral giredestrant plus everolimus or standard endocrine therapy plus everolimus; about 55% had ESR1 mutations.
• Follow-up: Median follow-up was 18.6 months.

Key Findings:

• Among patients with ESR1-mutated tumors, median PFS was 10 months with giredestrant plus everolimus versus 5.5 months with standard treatment, corresponding to a 63% lower risk of progression or death.
• In the intention-to-treat population, median PFS was 8.8 months with the giredestrant regimen versus 5.5 months with standard treatment, corresponding to a 44% lower risk of progression or death.
• Overall survival data were immature and described as trending favorably.
• The giredestrant regimen had a manageable safety profile consistent with the known profiles of the individual treatments.

Interpretation:

In the evERA study, giredestrant plus everolimus significantly improved PFS compared with standard endocrine therapy plus everolimus in both the ESR1-mutated and intention-to-treat populations.

Limitations:

• Overall survival data were immature at the time of reporting.

Conclusion:

In the phase 3 evERA study, giredestrant plus everolimus significantly improved median PFS compared with standard endocrine therapy plus everolimus in patients with advanced ER-positive, HER2-negative breast cancer, including those with ESR1-mutated tumors. Overall-survival data were immature at the time of reporting.