FDA clears AstraZeneca’s Etcamah for advanced breast cancer

AstraZeneca’s oral breast cancer drug Etcamah has secured accelerated approval from the US Food and Drug Administration for a defined group of patients with advanced disease, despite an earlier negative vote by the regulator’s oncology advisory panel.

The FDA authorised Etcamah, or camizestrant, with a CDK4/6 inhibitor for adults with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer when an ESR1 mutation is detected during treatment with an aromatase inhibitor and a CDK4/6 inhibitor. The mutation must be identified using an FDA-authorised test.

The decision gives AstraZeneca a significant regulatory win after the FDA’s Oncologic Drugs Advisory Committee voted 3-6 in April against the benefit-risk profile presented for the medicine. Six panel members opposed the application amid concerns over the design of the pivotal trial and uncertainty about whether switching treatment before radiographic disease progression would provide a meaningful long-term clinical benefit.

The FDA said the approval was granted under its accelerated approval pathway because camizestrant prolonged progression-free survival, an intermediate measure of benefit. The agency stressed, however, that it remains unconfirmed whether intervening immediately after detecting the resistance mutation, rather than waiting for confirmed disease progression, produces a clinically meaningful overall benefit. AstraZeneca will therefore be required to conduct confirmatory studies.

Angelo de Claro, director of the FDA’s Oncology Center of Excellence, said the decision marked the first FDA approval of a cancer treatment guided by detection of a resistance mutation in circulating tumour DNA before imaging showed the disease progressing. He added that further evidence was still needed to confirm clinical benefit.

The regulatory path remained uncertain after the advisory committee meeting. The FDA extended its review deadline in May to examine additional data requested from AstraZeneca. The agency had previously granted Breakthrough Therapy designation to the camizestrant combination in May 2025.

SERENA-6 also measured patient-reported health status. Median time to deterioration in global health status and quality of life was 21 months among patients switched to camizestrant, compared with 6.4 months for those who continued an aromatase inhibitor, according to the published study.

The approval rests on AstraZeneca’s Phase III SERENA-6 trial, which enrolled 315 eligible patients whose cancers developed an ESR1 mutation while they were receiving first-line treatment but had not yet progressed on scans. Patients were assigned either to switch from an aromatase inhibitor to camizestrant while continuing the same CDK4/6 inhibitor, or to remain on the existing aromatase inhibitor combination.

Median progression-free survival was 16 months for patients receiving camizestrant compared with 9.2 months for those who continued standard treatment. The trial showed a 56% reduction in the risk of disease progression or death, with a hazard ratio of 0.44. A later planned analysis also found median time to second disease progression of 25.7 months with camizestrant against 19.1 months in the comparator group. Overall survival data remain immature.

The New England Journal of Medicine, which published the trial results, reported that 3,256 patients were screened for ESR1 mutations and 315 qualified for randomisation. Discontinuation because of adverse events was uncommon, occurring in 1.3% of patients in the camizestrant arm and 1.9% of those remaining on an aromatase inhibitor.

ESR1 mutations are an important mechanism of acquired resistance to endocrine therapy. The FDA said fewer than 5% of patients have the mutation when hormone receptor-positive metastatic breast cancer is first diagnosed, but the proportion rises to nearly 40% after disease progression on an aromatase inhibitor. Detecting tumour DNA fragments in blood can reveal the mutation before conventional imaging shows worsening disease.

The regulator simultaneously authorised Guardant360 CDx as a companion diagnostic to identify eligible patients. AstraZeneca said the treatment strategy involves blood testing during routine tumour monitoring every two to three months, allowing clinicians to switch endocrine therapy when an ESR1 mutation emerges but before radiographic progression.

Etcamah is a next-generation oral selective oestrogen receptor degrader and complete oestrogen receptor antagonist. The recommended dose is 75mg once daily when used with palbociclib, ribociclib or abemaciclib.