The European Commission (EC) has approved AstraZeneca’s Etcamah (camizestrant) in combination with a Cyclin-Dependent Kinase (CDK) 4/6 inhibitor—palbociclib, ribociclib or abemaciclib—for the treatment of adult patients with Estrogen Receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer whose tumours develop ESR1 mutations during first-line endocrine therapy without disease progression.

The approval follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) and is based on findings from the pivotal Phase 3 SERENA-6 trial, published in The New England Journal of Medicine.

In the planned interim analysis, the Etcamah combination reduced the risk of disease progression or death by 56 percent compared with the current standard-of-care treatment comprising an aromatase inhibitor (anastrozole or letrozole) plus a CDK4/6 inhibitor. Patients receiving the Etcamah regimen achieved a median Progression-Free Survival (PFS) of 16.0 months, compared with 9.2 months in the control arm.

The approval introduces a new treatment strategy for patients whose tumours develop ESR1 mutations, a major mechanism of endocrine resistance that emerges in nearly 30 percent of patients with Hormone Receptor (HR)-positive breast cancer during first-line therapy. Detecting these mutations early allows clinicians to switch treatment before radiographic disease progression.

François-Clément Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie and Versailles University, and co-principal investigator of the SERENA-6 trial, said the approval represents a significant advancement for patients with advanced breast cancer by delaying disease progression and extending the benefits of first-line treatment. He also highlighted the clinical importance of circulating tumour DNA (ctDNA) monitoring for identifying ESR1 mutations before disease progression.

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said the approval marks a major shift in the treatment paradigm for ER-positive, HER2-negative advanced breast cancer by addressing treatment resistance before disease progression. He added that the decision reinforces AstraZeneca's commitment to delivering innovative therapies that improve patient outcomes.

The SERENA-6 trial is the first global Phase 3 registrational study to use a circulating tumour DNA (ctDNA)-guided approach to detect endocrine resistance through blood testing. The trial enrolled 315 patients with HR-positive, HER2-negative advanced breast cancer and demonstrated that switching endocrine therapy to Etcamah upon detection of ESR1 mutations—while continuing the same CDK4/6 inhibitor—significantly improved clinical outcomes.

Additional analyses also showed a statistically significant improvement in time to second disease progression (PFS2), extending median PFS2 to 25.7 months compared with 19.1 months for standard treatment. Overall survival data continue to mature, while the safety profile of the Etcamah combination remained consistent with the known safety profiles of the individual medicines, with no new safety concerns identified.

Etcamah has already received approvals in Japan, the United Arab Emirates and Saudi Arabia, while regulatory applications remain under review in several other countries, including the United States.

The approval strengthens AstraZeneca’s growing oncology portfolio and expands treatment options for patients with HR-positive, HER2-negative advanced breast cancer, the most common subtype of breast cancer worldwide.