Results from the phase 3 SERENA-6 trial revealed that switching from first-line treatment with an aromatase inhibitor to camizestrant after detection of an ESR1 mutation, while continuing with a CDK4/6 inhibitor, prolonged progression-free survival (PFS) among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2(HER2)-negative advanced breast cancer. 

These data were first presented by Nicholas Turner, MD, PhD, Royal Marsden Hospital, London, United Kingdom, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this double-blind study, researchers identified 3256 patients with HR-positive, HER2-negative advanced breast cancer treated in the first line setting with an aromataste inhibitor (anastrozole or letrozole) plus a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib). Patients underwent ctDNA testing for ESR1 mutations and routine imagining every 2 to 3 months and patients without evidence of disease progression (n = 315) were randomized on a 1-to-1 basis to receive 75 mg of camizestrant with continued CDK4/6 inhibition plus placebo (n = 157) or continued aromataste inhibition and CDK4/6 inhibition plus placebo (n = 158). The primary end point was PFS. Key secondary end points included overall survival (OS) and safety. 

At analysis, median PFS was 16 months in the camizestrant arm and 9.2 months in the continued aromatase inhibitor arm (hazard ratio [HR] 0.44; 95% confidence interval [CI], 24.9 to 42.2; P <.00001). The 12-month PFS rate was 60.7% in the camizestrant arm and 33.4% in the continued aromatase inhibitor arm. The 24-month PFS was 29.7% and 5.4%, respectively. The PFS2 HR was 0.52 and OS data were immature at analysis. Safety was consistent with prior findings. Treatment-related adverse events led to treatment discontinuation in 1.3% of patients in the camizestrant arm and 1.9% of patients in the continued aromatase inhibitor arm. 

“SERENA-6 is the first global phase 3 trial to demonstrate clinical utility of using ctDNA to detect and treat emerging resistance, ahead of disease progression,” concluded Dr Turner et al. “These findings represent a potential new treatment strategy to optimize and improve [first line] patient outcomes.”

Source: 

Turner NC, Mayer EL, Park YH, et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA4