Medical GIST therapy recommendations: KIT (CD117) & non PDGFRA-D842V-positive mutation:  • For patients progressing on imatinib 400 mg once daily, dosage should be increased to 400 mg twice daily.  • Sunitinib 50 mg once daily 4 weeks on 2 weeks off or 37.5 mg once daily continuously is the standard second-line therapy.  • Regorafenib 160 mg once daily 3 weeks on- 1 week off is the standard third-line therapy.  • Ripretinib 150 mg once daily is the standard fourth-line therapy.  • For patients progressing on fourth-line therapy, clinical trial enrolment, imatinib rechallenge, a continuation of TKI therapy or escalation of ripretinib to 150 mg twice daily can be considered.  • Clinical trial participation is encouraged if available throughout management. PDGFRA-D842V-positive mutation:  • For metastatic disease necessitating treatment, avapritinib 30–400 mg has demonstrated dramatic response rates. Wild-type GIST:  • The choice of systemic therapy should be individualized.