Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial

Peter Reichardt, George D. Demetri, Hans Gelderblom, Piotr Rutkowski, Seock Ah Im, Sudeep Gupta, Yoon Koo Kang, Patrick Schöffski, Jochen Schuette, Denis Soulières, Jean Yves Blay, David Goldstein, Kolette Fly, Xin Huang, Massimo Corsaro, Maria Jose Lechuga, Jean Francois Martini, Michael C. Heinrich

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Background: Several small studies indicated that the genotype of KIT or platelet-derived growth factor receptor-aα (PDGFRA) contributes in part to the level of clinical effectiveness of sunitinib in gastrointestinal stromal tumor (GIST) patients. This study aimed to correlate KIT and PDGFRA mutational status with clinical outcome metrics (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) in a larger international patient population. Methods: This is a non-interventional, retrospective analysis in patients with imatinib-resistant or intolerant GIST who were treated in a worldwide, open-label treatment-use study (Study 1036; NCT00094029) in which sunitinib was administered at a starting dose of 50 mg/day on a 4-week-on, 2-week-off schedule. Molecular status was obtained in local laboratories with tumor samples obtained either pre-imatinib, post-imatinib/pre-sunitinib, or post-sunitinib treatment, and all available data were used in the analyses regardless of collection time. The primary analysis compared PFS in patients with primary KIT exon 11 versus exon 9 mutations (using a 2-sided log-rank test) and secondary analyses compared OS (using the same test) and ORR (using a 2-sided Pearson χ2 test) in the same molecular subgroups. Results: Of the 1124 sunitinib-treated patients in the treatment-use study, 230 (20 %) were included in this analysis, and baseline characteristics were similar between the two study populations. Median PFS was 7.1 months. A significantly better PFS was observed in patients with a primary mutation in KIT exon 9 (n = 42) compared to those with a primary mutation in exon 11 (n = 143; hazard ratio = 0.59; 95 % confidence interval, 0.39-0.89; P = 0.011), with median PFS times of 12.3 and 7.0 months, respectively. Similarly, longer OS and higher ORR were observed in patients with a primary KIT mutation in exon 9 versus exon 11. The data available were limited to investigate the effects of additional KIT or PDGFRA mutations on the efficacy of sunitinib treatment. Conclusions: This large retrospective analysis confirms the prognostic significance of KIT mutation status in patients with GIST. This analysis also confirms the effectiveness of sunitinib as a post-imatinib therapy, regardless of mutational status.

Original languageEnglish (US)
Article number22
JournalBMC cancer
Issue number1
StatePublished - Jan 15 2016


  • GIST
  • Imatinib
  • Imatinib-resistant GIST
  • KIT
  • KIT mutation
  • Overall survival
  • Progression-free survival
  • Sunitinib

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research


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