AstraZeneca (LSE/STO/NYSE: AZN) has disclosed that the US FDA has extended the Prescription Drug User Fee Act (PDUFA) date for the New Drug Application (NDA) for camizestrant in combination with a CDK4/6 inhibitor, seeking first-line approval in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumours carry an emergent ESR1 mutation. The extension follows a request by the FDA for additional analyses to support its review.
The FDA had previously granted Breakthrough Therapy Designation for the camizestrant combination in this setting in May 2025. However, in April 2026, the agency's Oncologic Drugs Advisory Committee did not reach a majority vote in favour of the benefit of switching to camizestrant plus a CDK4/6 inhibitor upon detection of an ESR1 mutation in ctDNA prior to radiographic progression, a decision that preceded the current request for additional data.
The NDA, which covers camizestrant used alongside palbociclib, ribociclib, or abemaciclib, targets a molecularly defined patient population identified through circulating tumour DNA (ctDNA) testing during first-line treatment. The FDA's extension of the camizestrant PDUFA date was triggered by a request for supplementary data, including ctDNA clearance analyses linked to longer-term efficacy outcomes. AstraZeneca said those data are scheduled for presentation on June 2 at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. No revised PDUFA date was specified in the company's announcement.
SERENA-6 trial camizestrant data underpinning the application
The NDA is supported by the SERENA-6 Phase III trial, a double-blind, randomised study enrolling 315 adults with HR-positive, HER2-negative advanced breast cancer who were receiving first-line treatment with an aromatase inhibitor plus a CDK4/6 inhibitor and in whom an ESR1 mutation had emerged on ctDNA testing. Participants were randomised to switch the endocrine backbone to camizestrant or to continue with an aromatase inhibitor, in both cases alongside a CDK4/6 inhibitor.
The trial met its primary endpoint of investigator-assessed progression-free survival (PFS). Camizestrant reduced the risk of disease progression or death by 56% compared with continuing aromatase inhibitor therapy (HR 0.44; 95% CI 0.31–0.60; p < 0.00001), with median PFS of 16.0 months versus 9.2 months. Sustained disease control at 24 months was observed in 29.7% of patients in the camizestrant arm compared with 5.4% in the control arm. Data for the key secondary endpoints of overall survival and time to second disease progression (PFS2) were immature at the primary analysis, though PFS2 favoured camizestrant (25.7 months versus 19.1 months; HR 0.63; 95% CI 0.46–0.86; p=0.00373). Overall survival data showed an HR of 0.87 (95% CI 0.57–1.30) and continued to mature. Results were published in the New England Journal of Medicine in 2025 and presented at the ASCO Annual Meeting that year.
Scientific and competitive context
Camizestrant is an oral next-generation selective estrogen receptor degrader (SERD) and complete ER antagonist. ESR1 mutations arise in approximately 30% of patients with HR-positive advanced breast cancer during first-line aromatase inhibitor-based treatment, conferring ligand-independent ER activation and reducing the efficacy of continued aromatase inhibitor therapy. The camizestrant AstraZeneca approval filing is premised on a biomarker-guided adaptive strategy — switching the endocrine backbone upon ctDNA-detected ESR1 mutation emergence before radiographic progression — a clinical approach for which no therapy is currently approved.