pairingsPairing
CDK4/6 inhibitor + endocrine therapy
Cut the fuel (oestrogen) and jam the engine (CDK4/6) at the same time.
PFS roughly doubled and OS improved (MONALEESA, MONARCH 2) in advanced HR+ breast cancer; adjuvant benefit (NATALEE, monarchE). One of the most successful combinations in oncology.
Rationale
ER drives cyclin D1 transcription; CDK4/6 inhibition blocks the downstream engine so that residual ER signalling or ESR1 mutation cannot bypass it.
Evidence
Multiple phase 3 with OS benefit.