AstraZeneca plc (LON:AZN) 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 III trial presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.1
Kevin Kalinsky, MD, MS, FASCO, Division Director of Medical Oncology, Winship Cancer Institute of Emory University and investigator for the trial, said: “This combination provides an important new option for the one in three patients with this form of advanced breast cancer whose tumours 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.”
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Today’s approval is the tenth granted by the FDA this year across AstraZeneca’s portfolio and our fourth in breast cancer alone. The Etcamah combination reflects AstraZeneca’s leadership in redefining breast cancer care by pioneering a new approach using circulating tumour DNA and is the first and only medicine of its type in the 1st-line setting.”
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% versus standard-of-care treatment with an 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 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 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
In the US, breast cancer is the most common cancer in women, with more than 300,000 new patients diagnosed annually, and more than 42,000 deaths.2 Approximately 37,000 patients with HR-positive metastatic breast cancer in the US are treated with a medicine in the 1st-line setting, most frequently with endocrine therapies that target estrogen receptor (ER)-driven disease, which are often paired with CDK4/6 inhibitors.3-5 However, resistance to these therapies frequently develop in many patients.5 Once this occurs, treatment options are limited and survival rates are low with just over a third of patients anticipated to live beyond five years after diagnosis.5,6 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.7,8 Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1 mutations during 1st-line treatment before disease progression.3
Concurrently with this approval, the FDA also approved a companion diagnostic test to detect emerging ESR1 resistance mutations in the circulating tumour DNA (ctDNA) of patients with HR-positive, HER2-negative advanced or metastatic breast cancer. SERENA-6 is the first global, double-blind, registrational Phase III 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 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 more than 30 countries across the globe, including in the EU, Japan, Canada, the UK and several other countries based on the SERENA-6 Phase III 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.
- American Cancer Society. Key Statistics for Breast Cancer. Available at: https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html. Accessed September 2026.
- Cerner CancerMPact database. Accessed September 2026.
- Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944.
- Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5):821-30.
- National Cancer Institute. Cancer Stat facts: Female breast cancer subtypes. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed September 2026.
- Brett O, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor‑positive breast cancer. Breast Cancer Res. 2021; 23:85.
- Zundelevich A, et al. ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis. Breast Cancer Res. 2020; 22:16.
