Astrazeneca Plc (LON:AZN) has announced that Etcamah, in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor, has been approved in the European Union 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 1st-line endocrine therapy in combination with a CDK4/6 inhibitor.
Approval is based on SERENA-6 Phase III trial results, which showed the combination reduced the risk of disease progression or death by 56% in patients with an emergent ESR1 tumour mutation.
The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on the positive results from the pivotal SERENA-6 Phase III trial published in The New England Journal of Medicine.1
In a planned interim analysis, the Etcamah combination reduced the risk of disease progression or death by 56% 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% confidence interval [CI]:0.31-0.60; p<0.00001; median progression-free survival (PFS) 16.0 versus 9.2 months).
In Europe, breast cancer remains the leading cause of cancer death among women, with more than 140,000 deaths in 2024 and more than 540,000 patients diagnosed in the same year.2 Hormone receptor (HR)-positive breast cancer, characterised by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative.3 More than 97% of HR-positive breast cancer tumours are ER-positive.4,5 Across the UK, France, Germany, Spain and Italy, approximately 37,000 patients with HR-positive metastatic breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies paired with CDK4/6 inhibitors.6-8 However, many patients have tumours that develop resistance to these therapies, at which point treatment options are limited and survival rates are low, with only approximately 36% of patients anticipated to live beyond five years after diagnosis.3,8 Mutations in the ESR1 gene are a key driver of endocrine resistance and are associated with poor outcomes, emerging during treatment of the disease and becoming more prevalent as the disease progresses.9,10 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment before disease progression.6
François-Clément Bidard MD, PhD, Professor of Medical Oncology at Institut Curie & Versailles University (Paris/Saclay) France and co-principal investigator for the trial, said: “Today’s approval is welcome news for the one in three patients in Europe with this form of advanced breast cancer whose tumours develop ESR1 mutations before disease progression and are in urgent need of new options that both delay this progression and extend the benefit of 1st-line treatments. As the first pivotal trial to demonstrate the clinical value of monitoring circulating tumour DNA in the 1st-line breast cancer setting, SERENA-6 represents a significant advance in clinical practice and it is now important to identify patients who may be able to benefit from this combination and intervene promptly before their disease progresses.”
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “The approval of the Etcamah combination marks an important shift in the 1st-line treatment paradigm for patients with ER-positive, HER2-negative advanced breast cancer in Europe, providing a new standard-of-care to address emerging resistance ahead of disease progression. It also reflects the strength of AstraZeneca’s oncology pipeline and our commitment to translate innovative science into practice-changing treatment options for patients.”
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 of the SERENA-6 trial, however, a subsequent pre-planned analysis demonstrated a statistically significant and clinically meaningful PFS2 benefit of 25.7 months versus 19.1 months in favour of the Etcamah combination (HR: 0.63; 95% CI: 0.46-0.86; p=0.00373) and OS continued to mature in favour of the Etcamah combination (HR: 0.87; 95% CI: 0.57-1.30). The trial will continue to assess OS as a key secondary endpoint.
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.1
SERENA-6 is the first global, double-blind, registrational Phase III 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 tumour scans every two to three 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 Japan, the United Arab Emirates and Saudi Arabia based on the SERENA-6 Phase III trial. Regulatory applications for Etcamah in this setting are currently under review in several other countries including the US where the US Food and Drug Administration recently extended the Prescription Drug User Fee Act date to review the updated results from the trial.
References
- Bidard FC, et al. First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. N Engl J Med. 2025; DOI: 10.1056/NEJMoa2502929.
- World Health Organization. GLOBOCAN Europe Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf. Accessed July 2026.
- National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed July 2026.
- Bae S, et al. Poor prognosis of single hormone receptor positive breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer. 2015; 15:138.
- Cserni G, et al. Estrogen Receptor Negative and Progesterone Receptor Positive Breast Carcinomas-How Frequent are they? Pathol. Oncol. Res. 2011; 17:663-668.
- Cerner CancerMPact database. Accessed July 2026.
