FDA Approves Camizestrant Plus a CDK4/6 Inhibitor for Emergent ESR1-Mutated HR+, HER2– Advanced Breast Cancer

The FDA has granted accelerated approval to camizestrant (Etcamah) plus a CDK4/6 inhibitor (abemaciclib [Verzenio], palbociclib [Ibrance], or ribociclib [Kisqali]) for the treatment of adult patients with hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer that acquires an ESR1 mutation during aromatase inhibitor and CDK 4/6 inhibitor therapy, as identified by an FDA-approved test.^1,2

This regulatory decision was backed by data from the phase 3 SERENA-6 trial (NCT04964934) investigating the switch to oral camizestrant plus a CDK4/6 inhibitor vs continuing an aromatase inhibitor plus a CDK4/6 inhibitor.² The estimated median progression-free survival was 16 months (95% CI, 12.7-18.2) in the camizestrant arm (n = 157) vs 9.2 months (95% CI, 7.2-9.5) in the control arm (n = 158; HR, 0.44; 95% CI, 0.31-0.60; P < .00001).^2,3,4

Longer follow-up data presented at the 2025 San Antonio Breast Cancer Symposium put the median PFS values at 16.6 months (95% CI, 14.7-19.4) vs 9.2 months (95% CI, 7.2-9.7), respectively (HR, 0.46; 95% CI, 0.34-0.62; P < .00001).⁵

The FDA also approved the Guardant360 CDx assay as a companion diagnostic to identify patients with breast cancer harboring ESR1 mutations who may be eligible for treatment with camizestrant.²

“Women living with metastatic breast cancer face an uphill battle as their tumors continuously evolve to escape treatment. We owe them every weapon in our arsenal,” acting FDA Commissioner Kyle Diamantas, J.D., stated in a news release. “Today’s approval delivers a win to these patients by granting them a targeted therapy designed specifically to overcome resistance, giving them more time before their disease progresses.”

What was the regulatory path to the FDA approval of camizestrant for breast cancer with emergent ESR1 mutations?

In April 2026, the FDA’s Oncologic Drugs Advisory Committee voted 6 to 3 that SERENA-6 had not established clinically meaningful benefit for a ctDNA-triggered switch in this patient population; the agency separately told AstraZeneca that time to second progression (PFS2) would not stand as an efficacy end point supporting approval.⁶ At the FDA's request, the company filed supplementary evidence, including ctDNA clearance data linked to long-term outcomes, and the target action date for this approval was shifted.⁷

How was SERENA-6 designed?

Trial enrollment eligibility required ER-positive, HER2-negative advanced disease with no evidence of progression on an aromatase inhibitor plus a CDK4/6 inhibitor given as initial endocrine-based therapy, no prior chemotherapy for advanced disease, and a ctDNA-detected ESR1 mutation that was absent on radiographic progression.^3,4

The trial’s double-blind design randomly assigned patients 1:1 to receive camizestrant at 75 mg daily with their existing CDK4/6 inhibitor and an aromatase inhibitor placebo, or their unchanged aromatase inhibitor plus a CDK4/6 inhibitor with a camizestrant placebo. Imaging per RECIST 1.1 criteria ran every 8 weeks through 18 months, then every 12 weeks, with PFS2 scans mandated every 8 to 12 weeks. Investigator-assessed PFS was the primary end point; PFS2 and patient-reported outcomes were key secondary end points.

What did the SERENA-6 PFS2 and ctDNA analyses show?

Findings from additional analyses presented at ASCO 2026 showed that the median PFS2 reached 25.7 months (95% CI, 20.4-30.3) with camizestrant vs 19.1 months (95% CI, 16.8-21.0) with the control regimen (HR, 0.63; 95% CI, 0.46-0.86; P = .00373); the 30-month PFS2 rates were 41.5% and 29.7%, respectively.⁸ Findings from a RECIST 1.1 criteria–based supplementary analysis tracked closely with those results (HR, 0.64; 95% CI, 0.46-0.90; nominal P = .0094). The median chemotherapy/antibody-drug conjugate–free survival durations measured 22.6 months (95% CI, 19.3-30.9) vs 18.7 months (95% CI, 15.8-22.1), respectively (HR, 0.64; 95% CI, 0.47-0.87; nominal P = .00375).

The median PFS at 23.5 months of median follow-up stood at 16.8 months (95% CI, 14.7-19.4) vs 9.2 months (95% CI, 7.2-9.7), respectively (HR, 0.45; 95% CI, 0.34-0.59; nominal P < .00001). The PFS benefit with camizestrant switch vs control was sustained in patients with PIK3CA co-mutated (HR, 0.41; 95% CI, 0.26-0.64) and TP53 co-mutated disease (HR, 0.52; 95% CI, 0.31-0.88), as well as in patients with single (HR, 0.46; 95% CI, 0.34-0.62) and multiple ESR1mutations (HR, 0.48; 95% CI, 0.25-0.88).

The overall survival data stayed immature across all 3 respective data cutoff dates (HR, 0.91; 95% CI, 0.48-1.73; HR, 0.92; 95% CI, 0.57-1.48; and HR, 0.87; 95% CI, 0.57-1.30).2,3,4,7 The total ctDNA clearance rate hit 51.0% with camizestrant (n = 98) vs 1.9% with the control regimen (n = 108); the pooled clearance rates correlated with OS benefit (HR, 0.39; 95% CI, 0.19-0.73).7

References

1. FDA grants accelerated approval to a new breast cancer treatment. FDA. September 4, 2026. Accessed September 4, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-new-breast-cancer-treatment?utm_medium=email&utm_source=govdelivery
2. FDA grants accelerated approval to camizestrant with a CDK4/6 inhibitor for ESR1-mutated HR-positive, HER2-negative locally advanced or metastatic breast cancer. FDA. September 4, 2026. Accessed September 4, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-camizestrant-cdk46-inhibitor-esr1-mutated-hr-positive-her2-negative?utm_medium=email&utm_source=govdelivery
3. Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): phase 3, double-blind ctDNA-guided SERENA-6 trial. J Clin Oncol. 2025;43(suppl 17):LBA4. doi:10.1200/JCO.2025.43.17_suppl.LBA4
4. Bidard FC, Mayer EL, Park YH, et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med. 2025;393(6):569-580. doi:10.1056/NEJMoa2502929
5. Bidard FC, Mayer EL, Park YH, et al. Updated results and an exploratory analysis of ESR1m circulating tumor DNA dynamics from SERENA-6, a phase 3 trial of camizestrant + CDK4/6 inhibitor for emergent ESR1m during first-line endocrine-based therapy and ahead of disease progression in patients with HR+/HER2– advanced breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract RF7-03.
6. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Accessed May 27, 2026. https://www.youtube.com/live/taCx7enN7hk
7. US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data. News release. AstraZeneca. May 27, 2026. Accessed July 15, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/us-fda-decision-date-camizestrant-extended.html
8. Bidard F-C, Mayer E, Park YH, et al. First-line camizestrant for emergent ESR1 mutations in advanced breast cancer: final progression-free survival results 2 from the phase III SERENA-6 trial. J Clin Oncol. 2026;44(suppl 17):LBA1007. doi:10.1200/JCO.2026.44.17_suppl.LBA1007