SWITCHING to camizestrant upon detection of an ESR1 mutation, before clinical disease progression, may extend progression-free survival (PFS) for patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, according to results from the Phase III SERENA-6 trial.
The trial evaluated a targeted switch in therapy for patients undergoing first-line treatment with an aromatase inhibitor and a CDK4/6 inhibitor, a regimen commonly used in HR-positive, HER2-negative advanced breast cancer. In some patients, resistance to this combination arises due to mutations in the ESR1 gene, which encodes the estrogen receptor.
The SERENA-6 trial monitored 3,256 patients with advanced HR-positive, HER2-negative disease using circulating tumor DNA (ctDNA) testing every 2 to 3 months. Of these, 315 patients developed an ESR1 mutation before any radiographic disease progression. Patients were then randomized to either switch to the investigational selective estrogen receptor degrader (SERD) camizestrant (while continuing CDK4/6 inhibition) or continue with the existing aromatase inhibitor regimen.
Median PFS was significantly longer in the camizestrant arm, reaching 16.0 months versus 9.2 months in the control group. One- and two-year PFS rates also favored camizestrant (60.7% vs. 33.4% at one year; 29.7% vs. 5.4% at two years). These benefits were observed across multiple patient subgroups.
The trial also reported a longer duration of maintained quality of life in the camizestrant group. The side effect profile was consistent with known safety data for camizestrant, with few treatment discontinuations due to adverse events (1.3% vs. 1.9% in the control group).
While overall survival data remain immature, these findings suggest that early molecular monitoring for ESR1 mutations, followed by a targeted switch to camizestrant, may be a viable strategy to extend time to progression and preserve patient well-being during first-line treatment.
Reference:
American Society of Clinical Oncology (ASCO). Switching to Camizestrant After Detection of an ESR1 Mutation Improves Progression-Free Survival for Some Patients With Advanced Breast Cancer. 2025. Available at: https://www.asco.org/about-asco/press-center/news-releases/switching-camizestrant-after-detection-esr1-mutation-serena-6. Last accessed: 18 June 2025.
