Genentech: Giredestrant + everolimus improves PFS in ER‑positive advanced breast cancer (evERA Phase III, NEJM)

EvERA Phase III efficacy

Detailed evERA results published in The New England Journal of Medicine show giredestrant plus everolimus significantly improved investigator‑assessed progression‑free survival versus standard endocrine therapy plus everolimus in ER‑positive, HER2‑negative locally advanced or metastatic breast cancer post‑CDK4/6 inhibitor. In the ESR1‑mutated cohort median PFS was 10.0 versus 5.5 months (HR=0.38, 95% CI 0.27–0.54; p<0.001). In the intent‑to‑treat population median PFS was 8.8 versus 5.5 months (HR=0.56, 95% CI 0.44–0.71; p<0.001).

Survival trend and safety

Overall survival was immature at the time of analysis but showed a positive trend (ITT HR=0.69, 95% CI 0.47–1.00; ESR1‑mutated HR=0.62, 95% CI 0.38–1.02) with continued follow‑up planned. Adverse events were reported as manageable and consistent with known profiles of the individual agents; no unexpected safety signals were observed, including no photopsia and low rates of bradycardia.

Secondary endpoints and clinical implications

Additional analyses presented at the 2026 ASCO meeting indicated that giredestrant plus everolimus prolonged PFS2 (time to progression after second‑line therapy) and chemotherapy‑free survival versus standard endocrine therapy, suggesting the clinical benefit may extend beyond initial progression.

Regulatory status and trial context

evERA is a randomized, open‑label Phase III comparing giredestrant plus everolimus versus standard endocrine therapy plus everolimus in patients who progressed after CDK4/6 inhibitor and endocrine therapy. Based on these data, the FDA accepted an NDA for the combination in ESR1‑mutated locally advanced or metastatic disease with an expected decision by December 18, 2026, and accepted an adjuvant NDA under Priority Review with a PDUFA goal date of November 30, 2026.