AstraZeneca said the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of camizestrant in combination with a cyclin‑dependent kinase (CDK) 4/6 inhibitor (palbociclib, ribociclib or abemaciclib) for adults with estrogen receptor (ER)-positive, HER2‑negative locally advanced or metastatic breast cancer. The regimen is intended for use upon detection of an ESR1 mutation in patients whose disease has not yet progressed on first‑line endocrine therapy plus a CDK4/6 inhibitor.
The positive opinion is based on results from the pivotal SERENA‑6 Phase 3 trial, which were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine. In a planned interim analysis, the camizestrant combination reduced the risk of disease progression or death by 56% versus standard‑of‑care aromatase inhibitor (anastrozole or letrozole) plus a CDK4/6 inhibitor, corresponding to a hazard ratio of 0.44 (95% CI, 0.31–0.60; p<0.00001) and median progression‑free survival of 16.0 months versus 9.2 months.
Key secondary endpoints included time to second disease progression (PFS2) and overall survival. Although data were initially immature at the interim analysis, a subsequent pre‑planned analysis showed a statistically significant PFS2 benefit of 25.7 months versus 19.1 months with the camizestrant regimen (HR 0.63; 95% CI, 0.46–0.86; p=0.00373). Overall survival continued to mature in favor of camizestrant, with a hazard ratio of 0.87 (95% CI, 0.57–1.30), and the trial remains ongoing to further assess survival.
François‑Clément Bidard, MD, PhD, co‑principal investigator of SERENA‑6 and professor of medical oncology at Institut Curie & Versailles University, said the recommendation is an important step for patients in Europe and a milestone in new treatment strategies. He noted a need for approaches that delay progression in the first‑line setting, when disease is more manageable and quality of life is better, and said early intervention with the camizestrant combination at the time endocrine resistance emerges can extend the benefit of first‑line therapy and optimize outcomes.
Susan Galbraith, executive vice president, Oncology Haematology R&D at AstraZeneca, highlighted SERENA‑6 as the first pivotal trial to show the clinical value of using circulating tumor DNA (ctDNA) to detect emerging endocrine resistance and guide a change in treatment before radiographic progression. She said that, if approved, camizestrant would be the first next‑generation oral selective estrogen receptor degrader and complete ER antagonist to be used with widely approved CDK4/6 inhibitors in this first‑line setting, supporting a shift in clinical practice.
The safety profile of camizestrant plus palbociclib, ribociclib or abemaciclib in SERENA‑6 was consistent with the known profiles of the individual medicines, with no new safety concerns reported and low, similar discontinuation rates in both study arms. SERENA‑6 is described as the first global, double‑blind, registrational Phase 3 trial to use a ctDNA‑guided strategy to detect endocrine resistance via emerging ESR1 mutations and switch endocrine therapy before disease progression, while maintaining the same CDK4/6 inhibitor.
Camizestrant in combination with a CDK4/6 inhibitor is already approved in the United Arab Emirates and Saudi Arabia for hormone receptor‑positive, HER2‑negative advanced breast cancer with emergent ESR1 mutations, based on SERENA‑6 data. Regulatory submissions for this indication are under review in the United States, Japan and several other countries.
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