At a Glance
- Roche announced FDA acceptance of its giredestrant-everolimus NDA for ESR1-mutated advanced breast cancer.
- Phase 3 evERA trial showed 44% risk reduction overall and 62% in ESR1-mutated patients.
- Safety proved manageable with no new signals like photopsia.
- PDUFA date is December 18, 2026; lidERA submission pending.
Written By: Pharmacally Medical News Desk
Roche announced that the FDA has accepted its New Drug Application for Giredestrant combined with everolimus in ESR1-mutated, ER-positive, HER2-negative advanced breast cancer. This filing targets patients’ post-endocrine therapy and CDK4/6 inhibitors, with a decision expected by December 18, 2026.
Levi Garraway, Roche’s CMO, highlighted giredestrant’s clinical benefits as a potential new option to delay progression or death in advanced ER-positive breast cancer. He called the FDA acceptance a key first step toward making the giredestrant-everolimus combo a new standard of care.
evERA Trial
The phase III evERA trial (NCT05306340) drove the submission, showing giredestrant plus everolimus cut progression or death risk by 44% in the intention-to-treat population and 62% in ESR1-mutated patients versus standard endocrine therapy plus everolimus.
Median PFS reached 9.99 months versus 5.45 months in ESR1-mutated cases (HR=0.38, 95% CI: 0.27-0.54, p<0.0001) and 8.77 months versus 5.49 months overall (HR=0.56, 95% CI: 0.44-0.71, p<0.0001).
OS data remain immature but trend positive (ITT HR=0.69, p=0.0473; ESR1-mutated HR=0.62, p=0.0566), with ongoing follow-up. Safety aligned with known profiles of the drugs, with no new signals like photopsia.
Giredestrant Mechanism
Giredestrant, an oral next-generation SERD, blocks estrogen binding to ER, degrades the receptor, and halts cancer cell growth. Paired with everolimus (mTOR inhibitor), it targets dual pathways in endocrine-resistant disease, offering an all-oral option post-CDK4/6 inhibitors where up to 40% harbor ESR1 mutations.
Broader Development Program
evERA marks the first phase III win for giredestrant, followed by lidERA in early-stage disease; lidERA submission to FDA is pending. Ongoing trials include persevERA (first-line, readout H1 2026), pionERA, and heredERA across settings.
Trial | Setting | NCT ID | Combination |
lidERA | Adjuvant early-stage ER+/HER2- | NCT04961996 | Giredestrant vs SoC ET |
evERA | Post-CDK4/6 advanced | NCT05306340 | + Everolimus vs SoC ET + everolimus |
persevERA | First-line advanced | NCT04546009 | + Palbociclib vs letrozole + palbociclib |
pionERA | Adjuvant-resistant advanced | NCT06065748 | + CDK4/6i vs fulvestrant + CDK4/6i |
heredERA | ER+/HER2+ advanced | NCT05296798 | + Phesgo vs Phesgo |
Clinical Context
ER-positive breast cancer comprises 70% of cases, fueling 2.3 million diagnoses yearly amid rising resistance post-endocrine and CDK4/6 therapies. Oral SERD combos like this could shift standards by delaying progression without injections.
Reference
FDA accepts New Drug Application for Roche’s giredestrant in ESR1-mutated, ER-positive advanced breast cancer, 20 February 2026, FDA accepts New Drug Application for Roche’s giredestrant in ESR1-mutated, ER-positive advanced breast cancer
A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician’s Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer), ClinicalTrials.gov ID NCT05306340, https://clinicaltrials.gov/study/NCT05306340
Roche’s Phase 3 evERA Trial: Giredestrant Boosts Progression-Free Survival in ER-Positive Breast Cancer, 23 September 2026, https://pharmacally.com/roches-phase-3-evera-trial-giredestrant-boosts-progression-free-survival-in-er-positive-breast-cancer/