The European Commission has approved AstraZeneca’s Etcamah (camizestrant) with CDK4/6 inhibitors for ESR1-mutated ER-positive, HER2-negative advanced breast cancer after Phase 3 SERENA-6 reduced disease progression risk by 56%.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
AstraZeneca has secured European Commission approval for Etcamah (camizestrant) in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor for adults with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer whose tumors develop an ESR1 mutation during first-line endocrine therapy without disease progression.
The approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) and establishes Etcamah as the first next-generation oral selective estrogen receptor degrader (SERD) and complete estrogen receptor antagonist approved in the European Union for this treatment setting. It is also the only therapy approved for use with all three widely used CDK4/6 inhibitors: palbociclib, ribociclib, and abemaciclib. The decision was supported by results from the pivotal Phase III SERENA-6 trial, recently published in The New England Journal of Medicine.
Etcamah Delays Disease Progression in SERENA-6 Trial
The European approval was supported by strong efficacy data from the global Phase III SERENA-6 study (NCT04964934), which evaluated switching endocrine therapy after detecting an emergent ESR1 mutation through circulating tumor DNA (ctDNA) testing before radiographic disease progression.
At a planned interim analysis, Etcamah combined with a CDK4/6 inhibitor reduced the risk of disease progression or death by 56% compared with continued aromatase inhibitor therapy plus a CDK4/6 inhibitor (hazard ratio 0.44; 95% confidence interval [CI]: 0.31-0.60; p<0.00001).
Median progression-free survival reached 16.0 months with the Etcamah combination versus 9.2 months with standard treatment. A subsequent pre-planned analysis also demonstrated a statistically significant improvement in time to second disease progression (PFS2), extending median PFS2 to 25.7 months compared with 19.1 months (HR 0.63; 95% CI: 0.46-0.86; p=0.00373). Overall survival data remain immature but continue to trend in favor of Etcamah.
No new safety signals were observed. The safety profile of Etcamah combined with palbociclib, ribociclib, or abemaciclib was consistent with the known safety profiles of the individual therapies, and treatment discontinuation rates were low and similar between the study groups.
ctDNA-Guided Strategy Targets Resistance Before Disease Progression
SERENA-6 is the first global, double-blind, registrational Phase III trial to use circulating tumor DNA-guided monitoring to identify endocrine resistance before clinical disease progression.
The study enrolled 315 adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer receiving first-line treatment with an aromatase inhibitor and a CDK4/6 inhibitor. Blood samples collected during routine imaging every two to three months identified emerging ESR1 mutations before radiographic progression. Patients were then randomized to switch endocrine therapy from an aromatase inhibitor to Etcamah or continue the aromatase inhibitor while maintaining the same CDK4/6 inhibitor, allowing investigators to evaluate whether early intervention could delay disease progression.
The primary endpoint was investigator-assessed progression-free survival, with overall survival and PFS2 serving as key secondary endpoints.
Addressing a Common Driver of Endocrine Resistance
Hormone receptor-positive, HER2-negative breast cancer accounts for approximately 70% of all breast cancers, and more than 97% of these tumors express the estrogen receptor. Although endocrine therapy combined with CDK4/6 inhibitors remains the standard first-line treatment, approximately 30% of patients develop ESR1 mutations before disease progression, leading to endocrine resistance and poorer clinical outcomes.
Camizestrant is a potent, once-daily oral SERD that degrades and completely antagonizes the estrogen receptor, including receptors harboring activating ESR1 mutations. The recommended dose in combination with a CDK4/6 inhibitor is 75 mg once daily.
Experts Highlight a New First-Line Treatment Approach
SERENA-6 co-principal investigator Professor François-Clément Bidard said the approval provides an important option for patients whose tumors acquire ESR1 mutations before disease progression. He noted that the study validates routine ctDNA monitoring as a clinically meaningful strategy for identifying endocrine resistance early and intervening before treatment failure occurs.
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said the approval introduces a new first-line treatment approach that addresses emerging endocrine resistance before disease progression while extending the benefit of initial therapy.
Path Forward
The EU authorization marks another milestone for AstraZeneca’s oncology portfolio and represents the company’s 11th expected new medicine launch before 2030.
Etcamah has already received approvals in Japan, the United Arab Emirates, and Saudi Arabia based on the SERENA-6 trial. Regulatory applications remain under review in several countries, including the United States, where the FDA recently extended the Prescription Drug User Fee Act review timeline to evaluate updated clinical data.
Beyond SERENA-6, AstraZeneca is evaluating Etcamah in the Phase III SERENA-4, CAMBRIA-1, and CAMBRIA-2 trials across earlier-line and adjuvant hormone receptor-positive, HER2-negative breast cancer, supporting a broader strategy to move next-generation oral SERDs into earlier stages of treatment.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.