Kinase mutations and imatinib mesylate response for 64 Taiwanese with advanced GIST: preliminary experience from Chang Gung Memorial Hospital

Ann Surg Oncol. 2007 Mar;14(3):1123-8. doi: 10.1245/s10434-006-9288-1. Epub 2006 Dec 31.

Abstract

Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutation of kit or platelet-derived growth factor receptor alpha (PDGFRA), which are therapeutic targets for imatinib. Results of 64 Taiwanese with advanced GIST treated with imatinib were reported.

Method and materials: Between 2001 and May 2006, a prospective, non-randomized, and a single center trial containing 64 Taiwanese patients with advanced GIST treated with imatinib was conducted. Each tumor was investigated for mutations of kit or PDGFRA.

Results: The median follow-up time after imatinib administration was 16.1 months. 12 patients (18.8%) had complete response (CR), 24 (37.5%) had a partial response (PR), 12 stationary disease (18.8%), 16 progressive disease (25.0%). The 64 Taiwanese with advanced GIST had an estimated median survival of 48.0 months and 4-year survival rate for 76.1%. Kit mutation was found in 49 of 54 (90.7%) test patients and five of them had no mutation (9.3%). No PDGFRA mutant was identified. In 40 patients harboring kit exon 11 mutations, the CR and PR rates (ORR) were 57.5% , nine patients with tumors containing kit exon 9 mutation had ORR rates of 22.2%, and five patients with no mutation had ORR rates of 60.0% (not significant; P = 0.149).

Conclusions: Activated mutation of kit constituted 90.7% genetic alteration of Taiwanese with advanced GIST and no PDGFRA mutation was detected. Imatinib induced a sustained objective response in more than half of Taiwan advanced GIST patients. ORR did not differ between patients whose GISTs had no mutation, kit exon 9, and 11 mutations.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / secondary
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Imatinib Mesylate
  • Mutagenesis, Site-Directed
  • Mutation / genetics*
  • Piperazines / therapeutic use*
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins c-kit / genetics*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Pyrimidines / therapeutic use*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Survival Rate
  • Taiwan / epidemiology

Substances

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