giredestrant

Roche Reports Positive Phase III for Giredestrant Combo After CDK4/6 Progression

Roche’s Phase III evERA trial met its co-primary endpoints, with giredestrant + everolimus delivering significant PFS benefit in ER+/HER2- metastatic breast cancer after CDK4/6 inhibitor therapy. Results mark the first positive late-stage head-to-head study of an oral SERD regimen in this setting.

SDW Editor

— 1 min read

Roche announced positive Phase III results from the global evERA study, evaluating the oral selective estrogen receptor degrader (SERD) giredestrant in combination with everolimus for patients with oestrogen receptor (ER)-positive, HER2-negative metastatic breast cancer who had progressed following prior CDK4/6 inhibitor therapy.

Key Findings

  • Study Design: evERA (NCT05306340) is a randomized, open-label Phase III trial comparing giredestrant + everolimus (all-oral regimen) versus standard-of-care endocrine therapy + everolimus in patients with ER+/HER2- metastatic breast cancer.
  • Primary Endpoints: The trial met both co-primary endpoints, showing statistically significant and clinically meaningful improvements in progression-free survival (PFS) in the intention-to-treat (ITT) population and in patients with ESR1-mutated tumors.
  • Overall Survival (OS): Data remain immature, but Roche reported a positive trend. Longer follow-up is ongoing.
  • Safety: No new safety signals were observed. Adverse events were consistent with the known safety profiles of giredestrant and everolimus.

Why It Matters

  • First head-to-head Phase III success: This is the first positive late-stage trial of an all-oral SERD regimen combined with everolimus against standard endocrine therapy.
  • Addresses post-CDK4/6 resistance: Patients progressing after CDK4/6 inhibitors face limited options; the giredestrant combo offers a new potential standard of care.
  • Relevance of ESR1 mutations: Since ESR1 mutations drive resistance to aromatase inhibitors, these results support wider adoption of mutation testing to guide therapy.
  • Convenience for patients: An all-oral regimen may improve quality of life by reducing dependence on infusion centers.

Implications for China

  • CDK4/6 inhibitors (e.g. palbociclib, abemaciclib) are now widely used in China as first-line or early metastatic therapy. As resistance develops, demand for effective follow-on regimens is rising.
  • With Roche’s growing footprint in Chinese manufacturing and regulatory engagement, giredestrant + everolimus could be positioned quickly for local review and potential inclusion in clinical practice.
  • ESR1 mutation testing adoption in China is still developing, but this trial highlights its clinical utility, likely driving greater uptake in molecular diagnostics.

Next Steps

  • Roche will present the full evERA data at an upcoming medical meeting.
  • Regulatory discussions are planned with global health authorities.
  • Questions remain around overall survival benefit, reimbursement, and positioning relative to other emerging SERDs and targeted therapies.

References

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