Camizestrant in HR+/HER2– mBC: Emerging Data From the SERENA-6 Trial

SERENA-6 Trial Discussion and Clinical Implementation

The SERENA-6 trial represents a significant advancement in personalized breast cancer treatment through ctDNA monitoring for ESR1 mutations. In this innovative trial design, patients initially received an aromatase inhibitor plus CDK4/6 inhibitor in first-line treatment, with regular ctDNA testing to detect the emergence of ESR1 mutations. ESR1 mutations develop specifically as resistance mechanisms to estrogen deprivation therapy, making their detection crucial for treatment optimization.

When ESR1 mutations were detected, patients were randomly assigned to either continue their current aromatase inhibitor plus CDK4/6 inhibitor regimen or switch to oral SERD capivasertib while maintaining the same CDK4/6 inhibitor. The results showed median progression-free survival of approximately 16 months for patients who switched to capivasertib vs 9 months for those who remained on the aromatase inhibitor combination. This represents a clinically meaningful improvement in outcomes for patients with emergent ESR1 mutations.

Current clinical practice varies among oncologists regarding immediate implementation of these findings. Although some experts view the data as practice changing and have begun incorporating ESR1 mutation testing with treatment switches, others maintain their established second-line approach using fulvestrant plus PI3K pathway inhibitors. The consensus emphasizes the importance of secondary end points, including time to chemotherapy and overall survival data, to fully evaluate the clinical impact of this biomarker-driven strategy.