pairingsPairing
ctDNA KIT genotyping → TKI selection in GIST
A blood test that reads which resistance mutation a GIST has acquired, so the second drug can be chosen to fit it.
INTRIGUE showed ripretinib far outperformed sunitinib only in KIT exon 11 + 17/18 mutants, while sunitinib was better for exon 13/14; INSIGHT tested this prospectively with ctDNA selection (positive 2026). The first genotype-directed sequencing paradigm in sarcoma.
Rationale
Secondary KIT mutations are heterogeneous across metastases; plasma captures them all, and drug sensitivity differs by exon.
Evidence
Exploratory INTRIGUE analysis; prospective INSIGHT phase 3.