Many high-risk ER+HER2- breast cancers are now receiving first-line CDK4/6-inhibitors (e.g., palbociclib, ribociclib, or abemaciclib) in addition to aromatase inhibitors (AI). The prospective SERENA-6 trial performed ctDNA screening q2-3 months on 3256 women 6+ months into CDK4/6-inhibitor + AI. The 315 women who developed detectable ctDNA revealing an emergent ESR1 mutation without radiographic evidence of disease were then randomized 1:1 to continuing on first-line CDK4/6-inhibitor + AI versus switching to CDK4/6-inhibitor + camizestrant, a next-generation selective ER degrader and antagonist. The primary endpoint of clinical and or radiographic progression occurred at a median of 9 versus 16 months, respectively. This mirrors data reported nearly three years ago where a switch to fulvestrant significantly improved outcomes for these women. | Bidard, N Engl J Med 2025
