FDA advisory panel votes 3–6 against AstraZeneca’s camizestrant combination in first-line ESR1-mutant breast cancer despite positive SERENA-6 Phase III data
Written By: Vennela Reddy, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) voted against a favorable benefit-risk profile for AstraZeneca’s investigational therapy camizestrant, when used in combination with CDK4/6 inhibitors as a first-line treatment for hormone receptor (HR)-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations.
In a 3-6 vote, the committee did not support the regimen, although the FDA is not bound by ODAC recommendations and will make its own decision after reviewing the totality of the data.
The New Drug Application (NDA) for camizestrant in this setting was accepted by the FDA in July 2025, based on data from the Phase III SERENA-6 trial. The combination also received Breakthrough Therapy Designation in May 2025. AstraZeneca said it will continue to work with the agency as the review progresses.
Interim results from the SERENA-6 showed that switching to camizestrant plus a CDK4/6 inhibitor significantly improved outcomes versus aromatase inhibitor–based therapy, reducing the risk of disease progression or death by 56% (HR 0.44; 95% CI 0.31–0.60; p<0.00001) and extending median progression-free survival to 16.0 months compared with 9.2 months. Sustained disease control at 24 months was observed in 29.7% of patients versus 5.4%, while time to second progression (PFS2) also improved (25.7 vs 19.1 months; HR 0.63; p=0.00373). Overall survival data remain immature but trend in favor of the camizestrant arm, and patient-reported outcomes showed delayed deterioration in quality of life and symptoms, with a 46% reduction in risk compared with standard therapy.
The safety profile of camizestrant in combination with palbociclib, ribociclib, or abemaciclib was consistent with the known safety profiles of these agents. No new safety signals were identified, and treatment discontinuation rates were low and similar between both study arms.
Trial investigator Kevin Kalinsky said the results are meaningful for patients with limited treatment options and emphasized the need for therapies that delay progression earlier in the disease course. He described the committee’s decision as disappointing given the unmet need in this population.
Susan Galbraith Executive Vice President, Oncology Haematology R&D, AstraZeneca said the company acknowledged the committee’s mixed view but remained confident in the SERENA-6 findings, adding that camizestrant may improve outcomes by addressing resistance earlier in treatment.
HR-positive, HER2-negative breast cancer accounts for about 70% of breast cancer cases. Although endocrine therapy combined with CDK4/6 inhibitors remains standard first-line treatment, resistance often develops over time. ESR1 mutations are a major mechanism of resistance and emerge in roughly 30% of patients during first-line therapy.
Camizestrant remains under regulatory review in the U.S., European Union, Japan, and other markets. The FDA’s final decision will determine whether this ctDNA-guided treatment strategy becomes part of first-line management for patients with ESR1-mutant advanced breast cancer.
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About the Writer
Vennela Reddy, B Pharm is a pharmacy graduate with a keen interest in clinical research, pharmacovigilance, and medical writing, with a growing focus on publishable and scientific content development. In her words, she is passionate about translating complex medical data into clear, evidence-based communication.