Imatinib efficacy by tumor genotype in Korean patients with advanced gastrointestinal stromal tumors (GIST): The Korean GIST Study Group (KGSG) study

Acta Oncol. 2012 Apr;51(4):528-36. doi: 10.3109/0284186X.2011.636753. Epub 2011 Dec 7.

Abstract

Purpose: To assess the efficacy of imatinib for different tumor genotypes in Korean patients with advanced gastrointestinal stromal tumors (GIST).

Material and methods: Clinical data were collected from 370 consecutive patients with locally advanced unresectable, metastatic, or recurrent GIST treated with imatinib 400 mg/day between August 2001 and December 2007 at 20 Korean institutions. Tumor genotypes were determined for 290 patients by direct DNA sequencing of KIT exons 9, 11, 13, and 17, and PDGFRA exons 12, 14, and 18.

Results: Of 290 patients assessed for genotype, 261 (90.0%) had mutations in KIT: 222 (76.6%) in exon 11, 35 (12.1%) in exon 9 and two each (0.7%) for exons 13 and 17. Four patients (1.4%) had mutations in the PDGFRA gene: one in exon 12, and three in exon 18. Twenty-five patients (8.6%) had no detectable mutations. The best responses of the 235 patients with measurable lesions were: 15 complete response (6.4%), 126 partial response (53.5%), 86 stable disease (36.6%), and eight progressive disease (3.4%). Patients with KIT exon 9 mutations, compared with patients with KIT exon 11 mutations, had a lower objective response rate (36.7% vs. 63.6%, p = 0.007) and a shorter progression-free survival (median 28.7 months vs. 49.4 months, p = 0.001). No statistical difference in overall survival was observed between these genotypes.

Conclusion: This study confirms that imatinib efficacy is dependent on genotype in Korean GIST patients, consistent with results demonstrated by Western patients with GIST.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Exons / genetics
  • Female
  • Follow-Up Studies
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / mortality
  • Humans
  • Imatinib Mesylate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Piperazines / therapeutic use*
  • Prognosis
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / therapeutic use*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Retrospective Studies
  • Survival Rate
  • Young Adult

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha