CHMP issues positive opinion for AstraZeneca’s camizestrant plus CDK4/6 inhibitor in ESR1‑mutant, ER+/HER2‑ advanced breast cancer, backed by pivotal SERENA‑6 trial showing significant progression‑free survival benefit and ctDNA‑guided treatment switching.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending camizestrant in combination with a CDK4/6 inhibitor for adults with estrogen receptor‑positive, HER2‑negative locally advanced or metastatic breast cancer whose tumors acquire ESR1 mutations during first‑line endocrine therapy. The decision is based on pivotal Phase III SERENA‑6 (NCT04964934) results presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in The New England Journal of Medicine.
Novel SERD Strategy Against Endocrine Resistance
Camizestrant is an investigational next‑generation oral selective estrogen receptor degrader (SERD) and complete estrogen receptor antagonist. The therapy is designed to overcome endocrine resistance, a major challenge in hormone receptor‑positive breast cancer after prolonged exposure to aromatase inhibitors and CDK4/6 inhibitors. ESR1 mutations, which frequently emerge during treatment, are strongly associated with disease progression and poorer outcomes.
SERENA‑6 Trial Design and ctDNA‑Guided Switching
SERENA‑6 enrolled 315 patients with HR‑positive, HER2‑negative advanced breast cancer receiving first‑line aromatase inhibitor therapy plus a CDK4/6 inhibitor. Using routine blood‑based monitoring, investigators applied a circulating tumor DNA (ctDNA) strategy to detect emerging ESR1 mutations before radiographic progression. Patients with newly detected mutations switched endocrine therapy to camizestrant while continuing the same CDK4/6 inhibitor. This represents the first pivotal trial to validate ctDNA‑guided treatment switching in advanced breast cancer.
Efficacy Outcomes
In the planned interim analysis, camizestrant plus CDK4/6 inhibitor reduced the risk of progression or death by 56% compared with standard aromatase inhibitor therapy plus CDK4/6 inhibitor (HR 0.44; 95% CI 0.31–0.60; p<0.00001). Median progression‑free survival reached 16.0 months versus 9.2 months in the control arm.
A prespecified analysis also demonstrated a statistically significant improvement in progression‑free survival after second‑line therapy (PFS2). Median PFS2 was 25.7 months with camizestrant versus 19.1 months with standard treatment (HR 0.63; p=0.00373). Overall survival data remain immature but continue to trend in favor of the camizestrant arm.
Safety Profile
Investigators reported no new safety signals. The safety profile was consistent with known data for camizestrant and the partnered CDK4/6 inhibitors, with low discontinuation rates across both treatment arms.
Expert Commentary
François‑Clément Bidard, MD, PhD, co‑principal investigator of SERENA‑6, said the findings support earlier intervention against endocrine resistance before clinical progression occurs. AstraZeneca emphasized the trial as the first to demonstrate clinical benefit from ctDNA‑guided treatment switching in first‑line advanced breast cancer.
Regulatory Landscape
Camizestrant has already secured approvals in the United Arab Emirates and Saudi Arabia for this indication. Regulatory reviews are ongoing in the United States, Japan, and other global markets. The CHMP’s positive opinion positions the therapy for potential European approval, marking a significant step in advancing precision endocrine treatment strategies.
Reference
About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.