pairingsPairing
BRAF inhibitor + MEK inhibitor
Blocking two consecutive steps in the same relay prevents the pathway from rerouting and reduces side effects.
Dabrafenib-trametinib and encorafenib-binimetinib improved PFS and OS over BRAF inhibitor alone in melanoma and reduced paradoxical MAPK activation (fewer skin cancers). Template for vertical pathway inhibition.
Rationale
BRAF inhibitor monotherapy causes paradoxical MEK/ERK reactivation via CRAF dimers; adding MEK inhibition blocks the escape.
Evidence
Phase 3 OS benefit in melanoma; tumour-agnostic approval.