FDA approves AstraZeneca’s Etcamah combination for first line advanced HR positive breast cancer

The US Food and Drug Administration has granted accelerated approval to AstraZeneca’s Etcamah, or camizestrant, for use with a CDK4/6 inhibitor in a first line setting for certain patients with advanced breast cancer.

The approval covers adults with hormone receptor positive, HER2 negative locally advanced or metastatic disease who develop an ESR1 mutation while receiving an aromatase inhibitor together with a CDK4/6 inhibitor. The mutation must be confirmed using an FDA authorised test. Etcamah can be paired with abemaciclib, palbociclib or ribociclib.

The decision introduces a treatment strategy in which emerging endocrine resistance can be identified through circulating tumour DNA before conventional signs of disease progression appear. Patients can then switch endocrine therapy while continuing the same CDK4/6 inhibitor.

FDA clearance was supported by the Phase III SERENA-6 study, which evaluated this approach in patients whose ESR1 mutations emerged during treatment but whose cancer had not yet progressed clinically or radiographically. Results from the trial were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.

At a planned interim analysis, patients who switched from an aromatase inhibitor to Etcamah while remaining on their existing CDK4/6 inhibitor had a 56% lower risk of progression or death than those who continued standard treatment.

Median progression free survival was 16.0 months with Etcamah compared with 9.2 months among patients who remained on anastrozole or letrozole plus a CDK4/6 inhibitor. The hazard ratio was 0.44, with a 95% confidence interval of 0.31 to 0.60 and p<0.00001.

A later prespecified analysis also showed an advantage in time to second disease progression. Median PFS2 reached 25.7 months in the Etcamah arm versus 19.1 months with standard therapy, producing a hazard ratio of 0.63, a 95% confidence interval of 0.46 to 0.86 and p=0.00373.

Overall survival remained immature, although results continued to trend in favour of the Etcamah regimen. The hazard ratio was 0.87, with a 95% confidence interval of 0.57 to 1.30. Overall survival remains a key secondary endpoint and will continue to be followed.

Kevin Kalinsky, MD, MS, FASCO, Division Director of Medical Oncology at the Winship Cancer Institute of Emory University and an investigator in SERENA-6, said the approval creates an opportunity to intervene before patients experience clinical or radiographic progression.

He noted that around one third of patients with this type of advanced breast cancer develop ESR1 mutations during first line treatment and said identifying that resistance earlier could allow clinicians to alter therapy before the disease becomes more difficult to control and quality of life deteriorates.

AstraZeneca Oncology Haematology Business Unit Executive Vice President Dave Fredrickson said Etcamah represents the company’s fourth US breast cancer approval of the year and its tenth FDA approval across the wider portfolio in 2026. He described the ctDNA led treatment strategy as a new approach to first line breast cancer management.

No previously unrecognised safety issues were reported in SERENA-6. The tolerability of Etcamah when given with palbociclib, ribociclib or abemaciclib was in line with the established safety profiles of the individual treatments, while discontinuation rates were low in both treatment groups.

The SERENA-6 design centred on regular blood testing for circulating tumour DNA. Testing was carried out alongside routine tumour imaging every two to three months, allowing researchers to look for newly emerging ESR1 mutations before evidence of disease progression.

When an ESR1 mutation was found, patients assigned to the intervention group stopped their aromatase inhibitor and began Etcamah while continuing the same CDK4/6 inhibitor. This made SERENA-6 the first global double blind registrational Phase III study to use ctDNA findings to trigger a change in endocrine therapy ahead of progression.

The FDA also approved a companion diagnostic alongside Etcamah to identify emerging ESR1 resistance mutations in circulating tumour DNA from patients with HR positive, HER2 negative advanced or metastatic breast cancer.

ESR1 mutations are an established cause of resistance to endocrine treatment and tend to become more common as breast cancer advances. Around 30% of patients with endocrine sensitive HR positive disease are estimated to develop these mutations during first line therapy before progression is detected.

Approximately 37,000 patients with HR positive metastatic breast cancer in the US receive first line drug treatment, commonly involving endocrine therapy combined with a CDK4/6 inhibitor. Resistance remains a significant challenge, and once it develops, subsequent treatment options are more limited. Slightly more than one third of patients with metastatic disease are expected to survive for more than five years after diagnosis.

More broadly, breast cancer is the most commonly diagnosed cancer among women in the US, with more than 300,000 new cases and over 42,000 deaths each year.

Etcamah has also secured approvals in more than 30 countries on the strength of SERENA-6, including the UK, EU, Japan and Canada.

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AstraZeneca, Biopharma, breast cancer, Cancer, cancer research, Etcamah, FDA, FDA Approval, metastatic breast cancer, Oncology, pharmanews