The U.S. Food and Drug Administration (FDA) has granted accelerated approval to camizestrant in combination with a CDK4/6 inhibitor for adults with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose tumors develop an ESR1 mutation during treatment with an aromatase inhibitor and a CDK4/6 inhibitor.
The approval, announced on September 4, 2026, represents a notable shift in the treatment of advanced breast cancer: camizestrant is the first cancer therapy approved by the FDA based on detection of a resistance mutation in circulating tumor DNA (ctDNA) before radiographic disease progression.
Camizestrant is an oral selective estrogen receptor degrader (SERD) and complete estrogen receptor antagonist. Under the FDA indication, it may be combined with abemaciclib, palbociclib, or ribociclib. Patient selection is based on detection of an ESR1 mutation using an FDA-authorized test.
Targeting Endocrine Resistance Before Disease Progression
ESR1 mutations are an important mechanism of acquired resistance to endocrine therapy in HR-positive breast cancer. While fewer than 5% of patients have an ESR1 mutation when HR-positive metastatic breast cancer is initially diagnosed, the FDA noted that nearly 40% may have such mutations following progression on an aromatase inhibitor.
Unlike traditional treatment strategies that generally change therapy after clinical or radiographic progression, the camizestrant approach uses serial ctDNA monitoring to identify molecular resistance earlier and switch endocrine therapy while continuing CDK4/6 inhibition.
Angelo de Claro, Director of the FDA’s Oncology Center of Excellence, highlighted the regulatory significance of the decision:
“This marks the first FDA approval of a cancer therapy guided by the detection of a resistance mutation in circulating tumor DNA.”
The FDA simultaneously authorized Guardant360 CDx as a companion diagnostic to identify patients with ESR1-mutated breast cancer who may be eligible for camizestrant.
SERENA-6 Trial Supports Camizestrant Approval
The accelerated approval is based on findings from the Phase III SERENA-6 trial (NCT04964934), a global, randomized, double-blind study evaluating a ctDNA-guided treatment-switching strategy in patients receiving first-line therapy for HR-positive, HER2-negative advanced breast cancer.
Patients receiving an aromatase inhibitor plus a CDK4/6 inhibitor underwent serial blood testing for emerging ESR1 mutations. Those in whom an ESR1 mutation was detected before radiographic progression were randomized to either switch from the aromatase inhibitor to camizestrant while continuing their existing CDK4/6 inhibitor, or continue the aromatase inhibitor plus CDK4/6 inhibitor.
Among 315 randomized patients, median progression-free survival was:
- 16.0 months with camizestrant plus a CDK4/6 inhibitor
- 9.2 months with continued aromatase inhibitor plus a CDK4/6 inhibitor
Camizestrant reduced the risk of disease progression or death by 56% compared with continued aromatase inhibitor therapy (HR 0.44; 95% CI, 0.31–0.60; P<0.0001).
Longer follow-up subsequently showed median progression-free survival of 16.8 versus 9.2 months and a significant improvement in second progression-free survival, at 25.7 versus 19.1 months, respectively.
Safety and Accelerated Approval Requirements
The FDA prescribing information for camizestrant includes a boxed warning for the risk of cardiac arrhythmia when used with certain concomitant medications, as well as warnings concerning bradycardia and embryo-fetal toxicity.
Because the treatment was granted accelerated approval based on progression-free survival following molecular detection of resistance, continued approval may depend on confirmatory studies demonstrating clinical benefit. The FDA noted that it remains to be established whether switching treatment at molecular progression rather than waiting for radiographic progression ultimately translates into a meaningful long-term clinical benefit.
The regulatory decision follows an April 2026 meeting of the FDA’s Oncologic Drugs Advisory Committee, where the committee voted 3 to 6 on whether the benefit-risk profile supported the proposed treatment strategy.
The accelerated approval was granted to AstraZeneca.
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