KIT/PDGFRA Kinase Inhibitor (Specialist Oncology Drug)

Avapritinib

Brand names: Ayvakyt

Adult dose

Dose: Refer to BNF, SmPC, and current SACT protocol

Route: Oral

Frequency: As per SACT/MDT guidance

Clinical pearls

Indicated for: (1) unresectable or metastatic GIST with PDGFRA D842V mutation (any line); (2) unresectable or metastatic GIST with KIT exon 17/18 or PDGFRA exon 18 mutations after ≥1 prior TKI (4th line+)
NAVIGATE trial: high ORR (84%) in PDGFRA D842V GIST — historically resistant to imatinib
NICE TA741 (2021): avapritinib for PDGFRA D842V GIST
PDGFRA D842V mutation testing required before prescribing
Cognitive side effects (intracranial toxicity) are unique to avapritinib vs. other GIST TKIs — baseline cognitive assessment, use lowest effective dose
Take on empty stomach

Contraindications

See SmPC
CNS bleeding — avapritinib crosses blood-brain barrier; hold if intracranial haemorrhage

Side effects

Cognitive impairment (memory loss, confusion) — class effect; dose-dependent
Periorbital oedema
Nausea
Anaemia
Fatigue
Intracranial haemorrhage (rare but serious)

Interactions

Strong CYP3A4 inhibitors/inducers — affect avapritinib levels
See SmPC for complete interaction profile

Monitoring

Tumour response per SACT protocol (CT every 2–3 months)
Cognitive function / mental state at each visit
FBC
LFTs
Blood pressure
Periorbital oedema
MRI brain if any neurological symptoms

Reference: BNF; NICE TA741 (Avapritinib for PDGFRA D842V GIST, 2021); NAVIGATE trial (Lancet Oncol 2020); ESMO GIST Guidelines; https://bnf.nice.org.uk/drugs/avapritinib/. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways