Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis

Oncotarget. 2016 Oct 25;7(43):69412-69419. doi: 10.18632/oncotarget.5136.

Abstract

We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line.All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line.

Keywords: GIST; exon 11; imatinib; second line; sunitinib.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Exons / genetics*
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Mutation*
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrroles / therapeutic use*
  • Retrospective Studies
  • Sunitinib
  • Time Factors

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Sunitinib