FDA Approves Camizestrant for ESR1-Mutated Advanced Breast Cancer

The US Food and Drug Administration (FDA) has granted accelerated approval to camizestrant (Etcamah, AstraZeneca) in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) for adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer.

The approval targets tumors with emerging estrogen receptor-1 (ESR1) mutations detected during aromatase inhibitor (AI) and CDK4/6 inhibitor therapy.

The FDA also approved the Guardant360 CDx assay as a companion diagnostic to identify eligible patients via circulating tumor DNA (ctDNA) testing.

This is the first FDA approval of a cancer therapy guided by ctDNA resistance mutation detection before standard imaging demonstrates disease progression. This shifts clinical practice to an anticipatory adaptive approach.

To place this approval in context, HR-positive, HER2-negative disease is the most common breast cancer subtype, accounting for approximately 70% of cases. Endocrine therapies paired with CDK4/6 inhibitors are standard first-line treatments, but therapeutic resistance eventually develops. Mutations in the ESR1 gene drive this resistance and emerge in approximately 30% of patients during first-line therapy before clinical disease progression occurs.

The approval is based on the Phase III SERENA-6 trial (NCT04964934), a randomized, double-blind study of 315 adult patients with ER-positive, HER2-negative advanced breast cancer. Patients had received first-line AIs and CDK4/6 inhibitors for at least six months without disease progression. Upon ctDNA detection of an ESR1 mutation, patients switched to oral camizestrant (75 mg once daily) with continued CDK4/6 inhibitors or remained on standard therapy.

In the FDA-approved prescribing information, the investigator-assessed primary endpoint of median progression-free survival (PFS) was 16.0 months (95% CI, 12.7-18.2) in the camizestrant arm versus 9.2 months (95% CI, 7.2-9.5) in the control arm, reflecting a significant benefit (hazard ratio [HR], 0.44; 95% CI, 0.31-0.60; p < 0.00001).

Updated survival analyses from the 2026 American Society of Clinical Oncology Annual Meeting showed a median PFS of 16.8 months for camizestrant versus 9.2 months for standard care (HR, 0.45; 95% CI, 0.34-0.59; p < 0.00001), representing a 55% risk reduction. Long-term follow-up demonstrated that this PFS benefit was sustained beyond initial progression. The key secondary endpoint of second progression-free survival (PFS2) showed that camizestrant reduced the risk of second progression or death by 37% (HR, 0.63; 95% CI, 0.46-0.86; p = 0.00373), with a median PFS2 of 25.7 months versus 19.1 months.

The switch also delayed cytotoxic therapies. Median chemotherapy- or antibody-drug conjugate-free survival was 22.6 months for the camizestrant arm versus 18.7 months for the AI arm (HR, 0.64; 95% CI, 0.47-0.87; p = 0.00375).

In clinical practice, this framework relies on serial ctDNA blood testing every two to three months. In SERENA-6, switching to camizestrant led to a median 99% reduction in total ctDNA by week 8, and 51% of patients achieved complete ctDNA clearance (undetectable levels). Patients remaining on standard AI therapy had a median 64% increase in ctDNA, with 1.9% achieving clearance. Because clearance correlates with reduced tumor burden, nurses can leverage these biomarker trends to help patients visualize therapeutic efficacy.

The combination demonstrated a favorable safety profile, with discontinuation rates due to adverse events of 1.3% in the camizestrant arm and 1.9% in the control arm. The prescribing information contains a boxed warning for arrhythmia due to QTc interval prolongation when concomitantly used with QTc-prolonging drugs. Warnings and precautions also cover bradycardia and embryo-fetal toxicity.

References

1. Food and Drug Administration. 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. Published September 4, 2026. Accessed September 4, 2026.
2. 
   AstraZeneca. Camizestrant combination delayed time to first progression by 55% and to second progression by 37% in patients with advanced HR-positive breast cancer with an emergent ESR1 tumor mutation in SERENA-6 trial. Press release. Published June 2, 2026. Accessed June 2, 2026.
3. 
   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.
4. 
   Bidard FC, Barrios C, Bianchini G, et al. SERENA-6 interpretation and clinical implications: intercepting endocrine resistance in metastatic breast cancer. NPJ Breast Cancer. 2026;12(1):18.