FDA Extends Review of Camizestrant in ESR1‑Mutant Breast Cancer

The US Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) review timeline for AstraZeneca’s investigational oral selective estrogen receptor degrader (SERD) camizestrant in combination with CDK4/6 inhibitors. The application seeks approval for first-line treatment of hormone receptor (HR)-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations.

The extension follows the FDA’s request for additional analyses from the pivotal Phase III SERENA-6 trial supporting the New Drug Application (NDA). The FDA extended the PDUFA review timeline by several months, although a revised action date was not disclosed.

Trial Design and Outcomes

SERENA-6 enrolled 315 patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer receiving aromatase inhibitors plus CDK4/6 inhibitors as first-line therapy. Patients with emergent ESR1 mutations detected through circulating tumor DNA (ctDNA) monitoring switched from aromatase inhibitors to camizestrant while continuing CDK4/6 inhibition.

The primary endpoint was investigator-assessed progression-free survival (PFS), with secondary endpoints including overall survival and second progression-free survival (PFS2). Results presented at the 2025 ASCO Annual Meeting and published in The New England Journal of Medicine demonstrated significantly longer progression-free survival with early switching, without new safety signals.

ODAC Vote and Additional Analyses

The regulatory pathway became more complex after the FDA’s Oncologic Drugs Advisory Committee (ODAC) failed to reach a majority vote in April 2026, resulting in a 6-6 split on whether switching to camizestrant before radiographic progression provided sufficient clinical benefit to support approval.

In response, AstraZeneca submitted additional analyses, including ctDNA clearance data linked to longer-term efficacy outcomes. These findings will be presented at ASCO 2026 to further support the NDA.

Clinical Context

Camizestrant is a next-generation oral SERD and complete estrogen receptor antagonist that targets endocrine resistance in HR-positive breast cancer.

ESR1 mutations emerge in approximately 30% of patients receiving first-line endocrine therapy before radiographic progression. These mutations strongly correlate with endocrine resistance and poorer outcomes. Precision monitoring through ctDNA offers an opportunity to intervene earlier and extend the benefit of targeted endocrine therapies.

Global Regulatory Landscape

Despite the FDA delay, regulatory momentum continues internationally. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recently issued a positive opinion supporting approval of the camizestrant combination in this setting.

The therapy has already secured approvals in the United Arab Emirates and Saudi Arabia, while reviews remain ongoing in Japan and several additional markets. The divergence between US and EU regulatory positions underscores differing interpretations of ctDNA-guided treatment strategies.

Company Position

Susan Galbraith, Executive Vice President of Oncology Haematology R&D at AstraZeneca, said the company remains committed to advancing precision monitoring approaches that identify endocrine resistance earlier and extend patient benefit from targeted therapies.

 Reference

US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data