AstraZeneca’s camizestrant in combination with a Cyclin-Dependent Kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) has been recommended for approval in the European Union (EU) for the treatment of adult patients with Estrogen Receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer upon detection of ESR1 mutation and without disease progression during first-line endocrine therapy in combination with a CDK4/6 inhibitor.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on the results from the pivotal SERENA-6 phase 3 trial, which were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.

In a planned interim analysis, the camizestrant combination reduced the risk of disease progression or death by 56 percent versus standard-of-care treatment with an Aromatase Inhibitor (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 Progression-Free Survival (PFS) 16.0 versus 9.2 months). 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. However, 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 camizestrant combination (HR: 0.63; 95 percent CI: 0.46-0.86; p = 0.00373) and OS continued to mature in favor of the camizestrant combination (HR: 0.87; 95 percent CI: 0.57-1.30). The trial will continue to assess OS as a key secondary endpoint.

François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie and Versailles University (Paris/Saclay), France, and co-principal investigator for the SERENA-6 trial, said, “This recommendation represents an important step forward for patients with advanced breast cancer in Europe and a milestone in the adoption of new treatment strategies. There is a need for new treatments that delay disease progression in the first-line setting, after which the cancer becomes harder to treat, and a patient’s quality of life may decline. Through prompt intervention with the camizestrant combination to treat emergence of resistance before it causes disease progression and deterioration of quality of life, we are able to extend the benefit of first-line treatment and optimise outcomes.”

The safety profile of camizestrant 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.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said, “This decision from the EU’s CHMP is a vote of confidence in SERENA-6, the first pivotal trial to demonstrate the clinical value of monitoring circulating tumor DNA to detect emerging endocrine resistance and guide a change of therapeutic strategy in the first-line setting. If approved, camizestrant would be the first and only next-generation oral SERD and complete ER antagonist for use in combination with widely approved CDK4/6 inhibitors in this setting, reinforcing the practice-changing potential of this approach to advance patient outcomes and evolve the clinical landscape.”

SERENA-6 is the first global, double-blind, registrational phase 3 trial to use a circulating tumour DNA (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 camizestrant from ongoing treatment with an AI, while continuing combination with the same CDK4/6 inhibitor.

The camizestrant combination is approved in the United Arab Emirates (UAE) and Saudi Arabia in Hormone Receptor (HR)-positive, HER2-negative advanced breast cancer patients whose tumors have an emergent ESR1 mutation based on the results of the SERENA-6 phase 3 trial.

Regulatory applications for camizestrant in this setting are currently under review in the US, Japan and several other countries.