Discussion
GIST, advanced/metastatic PDGFRA D842V-mutant GIST, GIST bearing the PDGFRA D842V mutation, GISTs, Gastrointestinal Stromal Tumour
ONCOLOGY, GIST
Avapritinib (BLU-285) is a potent and selective small-molecule inhibitor that targets KIT proto-oncogene receptor tyrosine kinase (KIT) exon 17 and platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutations via type 1 inhibition.The safety and preliminary clinical efficacy of avapritinib for PDGFRA D842V-mutant GISTs were demonstrated in the global, phase I Avapritinib in Advanced PDGFRA D842V-mutant Gastrointestinal Stromal Tumour (NAVIGATOR) study.At data cutoff (January 8, 2021), 65 patients had received at least one avapritinib dose (12 patients in phase I, 53 in phase II), with 59 patients initially receiving avapritinib 300 mg (Patient characteristics.Time since initial diagnosis calculated by: (date of the first administration of treatment − date of the initial diagnosis + 1 day)/365.25 days.Abbreviations: ECOG, Eastern Cooperative Oncology Group; TKI, tyrosine kinase inhibitor; TNM, tumor-node-metastasis.Avapritinib had manageable safety and tolerability, consistent with NAVIGATOR. It demonstrated clinical benefit in Chinese patients with GIST bearing the PDGFRA D842V mutation and promising preliminary anti-tumor activity as fourth- or later-line monotherapy. Avapritinib demonstrated high anti-tumor activity (objective response rate [ORR] 79%) in patients with PDGFRA D842V-mutant GIST, suggesting that it may be effective in first-, or subsequent, lines of treatment in Chinese patients with advanced/metastatic PDGFRA D842V-mutant GIST, which represents a previously untreatable GIST subtype.