FDA Approves Camizestrant Plus CDK4/6 Inhibitor Following Emergence of ESR1 Mutation in Advanced Breast Cancer

Clinical Summary:

• The phase 3 SERENA-6 trial evaluated switching from an aromatase inhibitor to camizestrant while continuing CDK4/6 inhibition in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with an ESR1 mutation detected during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy and no evidence of disease progression.
• Switching to camizestrant plus continued CDK4/6 inhibition significantly prolonged progression-free survival compared with continuing an aromatase inhibitor plus CDK4/6 inhibition, reducing the risk of disease progression or death by 56%. Overall survival data were immature at analysis.  
• This approval introduces a biomarker-guided treatment strategy in which emerging ESR1 mutations can trigger a change in endocrine therapy before clinical disease progression, supporting serial ctDNA testing as a tool to guide treatment in HR-positive, HER2-negative advanced breast cancer. 

Based on results from the phase 3 SERENA-6 trial, the US Food and Drug Administration (FDA) granted accelerated approval to camizestrant (Etcamah; AstraZeneca) in combination with a CDK4/6 inhibitor for patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer following detection of an ESR1 mutation during aromatase inhibitor and CDK4/6 inhibitor therapy. 

In this double-blind, placebo-controlled trial, 315 patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer who developed a detectable ESR1 mutation during first-line treatment with an aromatase inhibitor and CDK4/6 inhibitor were randomized 1:1 to switch from the aromatase inhibitor to camizestrant while continuing their existing CDK4/6 inhibitor or to continue anastrozole or letrozole plus CDK4/6 inhibition. 

Patients were required to have received first-line treatment for ≥6 months without evidence of disease progression. ESR1 mutation status was assessed through blood-based ctDNA testing using the Guardant360 CDx assay. The primary end point was investigator-assessed progression-free survival (PFS). Key secondary end points included overall survival (OS) and safety. 

At analysis, median PFS was 16 months with camizestrant plus CDK4/6 inhibiton compared with 9.2 months with continued aromatase inhibitor plus CDK4/6 inhibiton. Switching to camizestrant reduced the risk of disease progression or death by 56% (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.31 to 0.6; P < .00001). OS data were immature at the time of PFS analysis. 

The recommended camizestrant dose is 75 mg once daily, with or without food, until disease progression or unacceptable toxicity. Treatment is administered in combination with abemaciclib, palbociclib, or ribociclib, with the CDK4/6 inhibitor continued at the same dosage being used when the ESR1 mutation was detected.

Prescribing information includes a boxed warning for the risk of arrhythmia due to QTc interval prolongation when used concomitantly with QTc interval-prolonging drugs. Additional warnings and precautions include bradycardia and embryo-fetal toxicity.

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.

Source:

US 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. Published online: September 4, 2026. Accessed on: September 8, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-camizestrant-cdk46-inhibitor-esr1-mutated-hr-positive-her2-negative