FDA Extends Action Date for Camizestrant in Advanced Breast Cancer

The FDA has extended the Prescription Drug User Fee Act (PDUFA) action date for the new drug application (NDA) of camizestrant. The extension allows the agency additional time to review supplementary data submitted to support the clinical use of the investigational drug in combination with a CDK4/6 inhibitor. The proposed indication targets the first-line treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer whose tumors present with an emergent ESR1 mutation.¹

The regulatory delay follows an April 2026 meeting of the FDA's Oncologic Drugs Advisory Committee (ODAC). During the session, the committee did not reach a majority vote supporting the clinical benefit of preemptively switching patients to the camizestrant combination after detecting an ESR1 mutation via circulating tumor DNA (ctDNA) prior to standard radiographic progression.² The initial NDA submission was built upon findings from the pivotal SERENA-6 phase 3 clinical trial (NCT04964934), which evaluated this specific early-intervention strategy.

“The biggest concern with the SERENA-6 trial is that approving the drug camizestrant would include an endorsement of a treatment paradigm that does not have established clinical benefit. It is unknown whether changing therapy at detection of an ESR1 mutation rather than waiting until radiography progression to start a new treatment improves long-term outcomes like overall for patients,” said Mirat Shah, MD, clinical team leader, Division of Oncology 1, Office of Oncologic Diseases, Office of New Drugs, FDA, during the ODAC meeting.

In response to the agency's requests and the advisory panel’s critique regarding trial design and definitive clinical endpoints, AstraZeneca provided additional statistical analyses.These supplementary data incorporate ctDNA clearance metrics correlated with longer-term clinical efficacy outcomes. The clinical community will receive a detailed look at these updated data on June 2 at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

SERENA-6 Study Background

The rationale behind evaluating camizestrant in this specific patient population stems from the molecular mechanisms of endocrine resistance. In the United States, approximately 37,000 patients with HR-positive metastatic breast cancer initiate first-line therapeutic regimens utilizing standard endocrine therapies combined with CDK4/6 inhibitors, including palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). Despite initial therapeutic efficacy, acquired resistance remains a significant barrier, with only 30% of patients with metastatic disease surviving 5 years postdiagnosis. Mutations within the ESR1 gene emerge in approximately 30% of these patients during first-line care, driving resistance to traditional aromatase inhibitors and serving as a molecular biomarker for poor prognostic outcomes.

The SERENA-6 phase 3 trial enrolled 315 adult patients to assess whether switching from an aromatase inhibitor to camizestrant—an oral, next-generation selective estrogen receptor degrader (SERD)—upon ctDNA detection of an ESR1 mutation could delay objective disease progression.The trial previously earned the combination an FDA breakthrough therapy designation in May 2025, following earlier data dissemination at the 2025 ASCO Annual Meeting and subsequent publication in The New England Journal of Medicine.³

“SERENA-6 is the first global registrational phase 3 study to demonstrate the clinical utility of circulating tumor DNA [ctDNA] monitoring to detect and treat emerging resistance ahead of disease progression,” Nicholas C. Turner, MD, PhD, lead study author and director of The Royal Marsden and Institute of Cancer and National Institute for Health and Care Research Biomedical Research Centre in London, United Kingdom, said during a presentation of the data at ASCO 2025.

Global Regulatory Actions for Camizestrant

While the US regulatory timeline has been extended, the global regulatory landscape for the agent reflects varying regional milestones.On May 22, 2026, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the marketing authorization of camizestrant for this exact clinical indication. Furthermore, the therapeutic combination has already secured regulatory approvals in the United Arab Emirates and Saudi Arabia, while parallel regulatory reviews remain ongoing before health authorities in Japan and multiple other countries.¹

REFERENCES

1. US FDA decision date extended for SERENA-6 filing of camizestrant to enable review of additional data. News release. AstraZeneca. May 27, 2026. Accessed May 27, 2026. https://tinyurl.com/3kzatcua

2. April 30, 2026 Meeting of the Oncologic Drugs Advisory Committee (ODAC). US FDA. Accessed May 27, 2026. https://tinyurl.com/yk8k3yws

3. Turner N, Mayer E, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. J Clin Oncol. 2025;43(suppl 17):LBA4. doi:10.1200/JCO.2025.43.17_suppl.LBA4