AstraZeneca's SERENA-6 Phase III trial demonstrated that camizestrant, in combination with a CDK4/6 inhibitor, significantly improved progression-free survival (PFS) in patients with HR-positive, HER2-negative advanced breast cancer with emergent ESR1 mutations, reducing the risk of disease progression or death by 56% compared to standard-of-care. The trial, which monitored circulating tumor DNA to detect resistance, also showed a meaningful delay in the deterioration of quality of life. These results support camizestrant's potential as a new standard-of-care endocrine therapy backbone in this setting, as it is the first oral SERD to demonstrate benefit in combination with CDK4/6 inhibitors in the 1st-line treatment.
AstraZeneca's SERENA-6 Phase III trial has yielded highly statistically significant and clinically meaningful results for camizestrant in combination with a CDK4/6 inhibitor for HR-positive, HER2-negative advanced breast cancer patients with emergent ESR1 mutations. The camizestrant combination demonstrated a 56% reduction in the risk of disease progression or death compared to standard-of-care (Hazard Ratio [HR] 0.44; 95% Confidence Interval [CI] 0.31-0.60; p<0.0001), extending median progression-free survival (PFS) to 16.0 months versus 9.2 months for the control arm. Notably, this is the first pivotal trial to successfully use circulating tumor DNA (ctDNA) monitoring to detect emerging resistance and guide a switch in therapy prior to observable disease progression. Furthermore, the camizestrant combination led to a meaningful delay in quality of life deterioration, reducing the risk by 47% (HR 0.53; 95% CI, 0.33-0.82; nominal p<0.0001), with a mean time to deterioration of 23.0 months versus 6.4 months. While overall survival (OS) data are immature, a positive trend was observed for time to second disease progression (PFS2) (HR 0.52; 95% CI 0.33-0.81; p=0.0038, though the interim analysis threshold was p=0.0001). The safety profile was consistent with known profiles of the individual drugs; Grade 3 or higher adverse events occurred in 60% of camizestrant arm patients versus 46% in the AI arm, primarily hematological and linked to CDK4/6 inhibitors, but discontinuation rates were low and similar (1% for camizestrant, 2% for AI). These findings, leading to an FDA Breakthrough Therapy Designation, position camizestrant as a potential new standard-of-care endocrine therapy backbone in this 1st-line setting, being the first next-generation oral SERD to show such benefit.
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