pairingsPairing
Oral SERD + CDK4/6 inhibitor after ESR1 emergence
When an ESR1 mutation appears, swap the aromatase inhibitor for an oral SERD and keep the CDK4/6 inhibitor going.
SERENA-6 (camizestrant switch at ctDNA ESR1 emergence, PFS HR 0.44) and EMBER-3 (imlunestrant + abemaciclib, PFS HR 0.57) show oral SERDs partner well with CDK4/6 inhibitors in resistance settings. Upfront replacement of the AI without selection failed (persevERA).
Rationale
ESR1 mutations make ER ligand-independent, neutralising AIs but not degraders; CDK4/6 dependence persists.
Evidence
Two positive phase 3 trials; FDA accelerated approval (camizestrant) 2026.