Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib: relationship between efficacy and tumor genotype in Korean patients

Invest New Drugs. 2012 Apr;30(2):819-27. doi: 10.1007/s10637-010-9593-1. Epub 2010 Nov 23.

Abstract

Background: To assess the efficacy and safety of sunitinib with regards to primary genotypes of tumor in Korean patients with advanced gastrointestinal stromal tumors (GISTs) who failed an initial therapy of imatinib.

Methods: Clinical data were collected from 88 consecutive patients with metastatic/unresectable GISTs treated with sunitinib at the Asan Medical Center.

Results: The median time-to-progression (TTP) and overall survival (OS) times were 7.1 months and 17.6 months, respectively. Of the 74 patients tested for KIT (exons 9, 11, 13, 17) and PDGFRA (exons 12 and 18), patients with KIT exon 9 mutant GIST (n = 11, 14.9%) showed numerically better clinical benefit (objective response or stable disease ≥ 24 weeks) rate (63.6% vs 46.8%, p = 0.504) and TTP (median 13.6 mo vs 6.9 mo, p = 0.631) than those with KIT exon 11 mutant GIST (n = 47, 63.5%). The most common grade 3/4 adverse events included neutropenia (34.1%), thrombocytopenia (33.0%) and hand-foot skin reaction (25.0%).

Conclusions: Sunitinib is an effective and safe second-line therapy for Korean patients with advanced GIST. The superior efficacy of sunitinib against GISTs with KIT exon 9 mutations appears to be similar in Korean patients to Western experience although statistical significance was not secured.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Asian People / genetics
  • Benzamides
  • Chi-Square Distribution
  • DNA Mutational Analysis
  • Disease Progression
  • Disease-Free Survival
  • Exons
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / enzymology
  • Gastrointestinal Stromal Tumors / ethnology
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / mortality
  • Gastrointestinal Stromal Tumors / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Imatinib Mesylate
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Multivariate Analysis
  • Mutation
  • Phenotype
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sunitinib
  • Time Factors
  • Treatment Failure

Substances

  • Antineoplastic Agents
  • Benzamides
  • Indoles
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha
  • Sunitinib