SERENA-6 Trial Design and Primary Efficacy Data

Rebecca Shatsky, MD, walks through the design of the phase 3 SERENA-6 trial, led by Francois Bedard, who also designed the earlier PADA-1 trial using fulvestrant. Over 3,325 women with hormone receptor-positive, HER2-negative metastatic breast cancer on first-line aromatase inhibitor plus CDK4/6 inhibitor therapy were screened for ESR1 mutations every 2 to 3 months using a Guardant360 ctDNA assay. Patients without radiographic progression were randomized to continue their aromatase inhibitor and CDK4/6 inhibitor or switch to camizestrant plus a CDK4/6 inhibitor. Dr. Shatsky reports that patients who stayed on original therapy had a median progression-free survival of about 9 months, compared with almost 17 months in the camizestrant switch group, a roughly 7-month difference favoring early molecular-guided switching. Neil Iyengar, MD, notes the trial met its primary endpoint despite debate over how progression-free survival should be counted in a molecularly guided strategy.