OnCo
pairingsPairing

PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)

Blocking the PI3K growth pathway alongside hormone therapy works only when the tumour carries a mutation in that pathway, and works best early.

SOLAR-1 (alpelisib), CAPItello-291 (capivasertib), and INAVO120 (inavolisib with palbociclib and fulvestrant; OS HR 0.67) all show benefit restricted to, or largest in, PIK3CA/AKT1/PTEN-altered tumours. Toxicity (hyperglycaemia, rash, diarrhoea) differs by agent and shapes choice.

Rationale
PI3K pathway activation is a dominant escape from ER dependence; combined blockade removes both survival inputs.
Evidence
Three positive phase 3 trials with biomarker selection.

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