AstraZeneca’s ETCAMAH (camizestrant) in combination with a Cyclin-Dependent Kinase (CDK) 4/6 inhibitor (abemaciclib, palbociclib or ribociclib) has been approved in the US for the treatment of adult patients with Hormone Receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer upon detection of ESR1 mutation during Aromatase Inhibitor (AI) and CDK4/6 inhibitor therapy, based on a US Food and Drug Administration (FDA)-authorised test.

The accelerated approval was based on results from the pivotal SERENA-6 phase 3 trial presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.

Kevin Kalinsky, MD, MS, FASCO, Division Director, Medical Oncology, Winship Cancer Institute of Emory University and investigator for the trial, said, “The combination provides an important new option for the 1 in 3 patients with this form of advanced breast cancer whose tumors develop ESR1 mutations before clinical or radiographic disease progression. Today’s approval will enable clinicians to promptly intervene and change therapeutic strategy at an earlier opportunity ahead of disease progression, rather than waiting until the cancer becomes harder to treat, and patient outcomes and quality of life worsen.”

In a planned interim analysis of the SERENA-6 trial, ETCAMAH in combination with a CDK4/6 inhibitor reduced the risk of disease progression or death by 56 percent versus Standard-of-Care (SoC) treatment with an AI (anastrozole or letrozole) in combination with a CDK4/6 inhibitor (based on a hazard ratio [HR] of 0.44; 95 percent Confidence Interval [CI]:0.31-0.60; p<0.00001; median PFS 16.0 versus 9.2 months).

While data for the key secondary endpoints of time to second disease progression (PFS2) and Overall Survival (OS) were immature at the time of the interim analysis, a subsequent pre-planned analysis demonstrated a statistically significant and clinically meaningful PFS2 benefit of 25.7 months versus 19.1 months in favor of the ETCAMAH combination (HR: 0.63; 95 percent CI: 0.46-0.86; p=0.00373) and OS continued to mature in favor of the ETCAMAH combination (HR: 0.87; 95 percent CI: 0.57-1.30). The trial will continue to assess OS as a key secondary endpoint.

Dave Fredrickson, Executive Vice President (EVP), Oncology Haematology Business Unit, AstraZeneca, said, “Today’s approval is the 10^th granted by the FDA this year across AstraZeneca’s portfolio and our 4^th in breast cancer alone. The ETCAMAH combination reflects AstraZeneca’s leadership in redefining breast cancer care by pioneering a new approach using circulating tumor DNA and is the first and only medicine of its type in the first-line setting.”

The safety profile of ETCAMAH in combination with palbociclib, ribociclib or abemaciclib in the SERENA-6 trial was consistent with the known safety profile of each medicine. No new safety concerns were identified, and discontinuations were very low and similar in both arms.

Concurrently with this approval, the FDA also approved a companion diagnostic test to detect emerging ESR1 resistance mutations in the circulating tumor DNA (ctDNA) of patients with HR-positive, HER2-negative advanced or metastatic breast cancer.

SERENA-6 is the first global, double-blind, registrational phase 3 trial to use a ctDNA-guided approach to detect the emergence of endocrine resistance and inform a switch in therapy before disease progression. The innovative trial design used ctDNA monitoring via a blood test at the time of routine tumor scans every 2 to 3 months to identify patients for early signs of endocrine resistance via the emergence of ESR1 mutations. Following detection of an ESR1 mutation without disease progression, the endocrine therapy of patients was switched to ETCAMAH from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor.

ETCAMAH is also approved in over 30 countries across the globe, including in the European Union (EU), Japan, Canada, the UK and several other countries based on the SERENA-6 phase 3 trial.