Genomic Subtypes of GISTs for Stratifying Patient Response to Sunitinib following Imatinib Resistance: A Pooled Analysis and Systematic Review

OBJECTIVES: Sunitinib (a second-line chemotherapeutic agent that inhibits multiple kinases, including KIT and PDGFR) is widely used in imatinib-resistant patients with gastrointestinal stromal tumors (GISTs). However, diverse responses to sunitinib have been observed in the clinic. We aimed to evaluate whether the different GIST genotypes could be used to stratify patient response to sunitinib. METHODS: We searched the PubMed, Embase, and Cochrane databases and included English-language literature published up to August 31, 2017. Inclusion criteria were GIST patients with KIT exon 9, KIT exon 11, or PDGFRA mutations and those without KIT/PDGFRA mutations (termed the wild-type genotype) who were receiving sunitinib within a clinical trial, and the efficacy evaluation was clinical benefit rate (CBR), median progression-free survival (PFS), and overall survival (OS). Odds ratios (ORs) for CBR and hazard ratios (HRs) for PFS and OS with 95% confidence intervals (CIs) in sunitinib-treated GIST patients with different genotypes were compared. RESULTS: Seven studies totaling 531 patients were included. Patients with KIT mutations showed an improved CBR to sunitinib compared to those with PDGFRA mutations. In particular, those with the KIT exon 9 or 11 mutation showed improved CBR over those with PDGFRA mutation. Moreover, GIST patients with the KIT exon 9 mutation showed improved CBR over those with the KIT exon 11 mutation. Patients without KIT/PDGFRA mutations (wild-type genotype) showed better CBR than those with PDGFRA mutations. CONCLUSION: GIST genotypes may be useful for stratifying patient response to sunitinib after imatinib resistance.