camizestrant Shows Promise for ESR1-Mutated Breast Cancer

‍ Updated June 05, 2025

Chicago—AstraZeneca’s camizestrant, when paired with a CDK4/6 inhibitor, considerably improved progression-free survival (PFS) in patients with Esr1-mutated, hormone ⁣receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. The findings, presented at the 2025 ⁤American Society ‍of Clinical Oncology meeting, suggest a potential new first-line treatment strategy.

The SERENA-6 trial (NCT04964934) explored a ctDNA-guided approach, detecting Esr1 mutations during initial treatment with an aromatase inhibitor and a CDK4/6 inhibitor. patients without disease progression were then randomly assigned to either switch to camizestrant while ‍continuing the CDK4/6 inhibitor or continue their original aromatase inhibitor regimen.

The study enrolled patients with HR+/HER2- advanced breast cancer who had previously received at least six months of first-line treatment with an aromatase inhibitor (anastrozole or letrozole) combined with a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib). Researchers ⁢tested ctDNA for Esr1 mutations every two to three months, coinciding with routine⁤ imaging.

the primary endpoint of SERENA-6 was investigator-assessed ⁣PFS. Secondary endpoints included overall survival (OS), chemotherapy-free survival, ‍objective response rate (ORR), and clinical benefit rate. The data cutoff for the interim analysis was Nov. 28, 2024.

Of ⁢3,256 patients screened, 315 were randomly assigned to switch to camizestrant (n=157) or continue their aromatase inhibitor (n=158), while maintaining their CDK4/6 inhibitor. Approximately 50% of randomly assigned patients had Esr1 ⁤mutations ⁢detected at the initial⁣ ctDNA test.

After 171 PFS events,⁤ the hazard ‍ratio (HR) for PFS ⁣was approximately 0.44 ⁢(95% CI 0.31–0.60, p < .00001), with a median PFS of 16.0 months versus 9.2 months. This translates to a roughly 56% reduction in the risk of disease progression or death compared to standard treatment. The 12-month PFS rate was about 60.7% versus 33.4%, and ‍the⁤ 24-month rates were 29.7% versus 5.4%. Overall survival data were immature at the time of analysis.

“[The SERENA-6 findings] mark a pivotal moment in breast cancer care and redefine how we think about drug resistance in this type of breast cancer…This proactive approach exemplifies a new treatment strategy in oncology,” said ⁣Dr.Nicholas Turner, professor of molecular oncology at the Institute of ⁣Cancer Research, London.

The safety profile of camizestrant ‍combined with a CDK4/6 inhibitor aligned with the known profiles of each drug. Common ⁤adverse events (AEs) were hematological, including neutropenia (45% camizestrant vs. 34% standard of care), anemia (5% in both groups), and leukopenia (10% vs.3%). Treatment discontinuation rates due to⁤ AEs were low, at approximately 1.3% for camizestrant and 1.9% for aromatase inhibitors.

“As the first pivotal trial to demonstrate the clinical value of monitoring ctDNA to detect emerging resistance and change therapy at the earliest chance; SERENA-6 is redefining the clinical paradigm in breast cancer,” said Susan Galbraith, executive vice president of oncology and‍ hematology research and development ⁣at astrazeneca.

What’s next

Further studies will continue to assess the long-term⁣ benefits of camizestrant in treating advanced ⁢breast cancer,‍ notably focusing on overall survival and quality of life improvements.