Switching to treatment with camizestrant if an ESR1 mutation is detected during first-line treatment can help slow cancer growth for patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, according to findings from the phase III SERENA-6 clinical trial. The research is being presented during the Plenary Session at the 2025 ASCO Annual Meeting (Abstract LBA4).
Study Details
Patients with HR-positive, HER2-negative advanced breast cancer often receive hormone therapy—most commonly an aromatase inhibitor—as their first-line treatment given in combination with a CDK4/6 inhibitor. However, some cancers become resistant to this treatment, with the most common culprit being ESR1 mutations.
Although testing for ESR1 mutations is common in patients receiving an aromatase inhibitor and CDK4/6 inhibitor, the testing is typically not performed until the cancer has already started to grow during treatment. There are other treatments for patients whose cancer has progressed on first-line treatments, but survival rates are low, and there is a decreased quality of life.
Camizestrant, a selective estrogen receptor degrader, works by inhibiting and breaking down estrogen receptors. Although it is still in the investigational stage, it has shown promise in treating patients regardless of whether they have ESR1 mutations. In the SERENA-6 clinical trial, researchers sought to determine whether switching to camizestrant upon detection of an ESR1 mutation—but before their disease started to spread—might slow their cancer growth.
SERENA-6 enrolled 3,256 patients with HR-positive, HER2-negative advanced breast cancer who had received at least 6 months of treatment with an aromatase inhibitor and a CDK4/6 inhibitor. Patients had their circulating tumor DNA (ctDNA) tested for ESR1 mutations every 2 to 3 months until 315 patients developed ESR1 mutations before disease progression. About 50% of these patients had an ESR1 mutation detected during the first ctDNA test.
These 315 patients were randomly assigned to either switch to camizestrant, continuing with the CDK4/6 inhibitor and adding a placebo in place of the aromatase inhibitor (n = 157), or continue treatment with the aromatase inhibitor and CDK4/6 inhibitor, adding a placebo in place of camizestrant (n = 158).
Key Findings
Median progression-free survival was 16 months for those patients who switched to camizestrant vs 9.2 months for those who continued treatment with an aromatase inhibitor. This improvement was seen across different subgroups of patients.
The progression-free survival rate 1 and 2 years after treatment was also significantly higher in the camizestrant group. At 1 year, progression-free survival was 60.7% in the camizestrant group vs 33.4% in the aromatase inhibitor group. Overall survival benefit has yet to be determined, as these data were immature at the time of the analysis.
Side effects in the camizestrant group were consistent with previously known side effects of the drug, and no new side effects were reported.
Breakthrough Therapy Designation
Based on the results of SERENA-6, AstraZeneca announced on June 1 that camizestrant in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of adult patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer upon emergence of an ESR1 mutation during first-line endocrine-based therapy.
Conclusion
According to Eleonora Teplinsky, MD, Head of Breast and Gynecologic Medical Oncology at Valley-Mount Sinai Comprehensive Cancer Care and an ASCO Expert in breast cancer, “The early switch approach of the SERENA-6 clinical trial resulted in a 56% reduction in the risk of disease progression or death for patients who switched to treatment with camizestrant, allowing patients to stay on first-line therapy for a longer period of time. Camizestrant is not yet FDA approved, but these data will likely pave the way for a new treatment paradigm in first-line therapy for HR-positive, HER2-negative advanced breast cancer.”
Disclosure: This study was funded by AstraZeneca. For full disclosures of the study authors, visit coi.asco.org.
