Long-term survival outcome with tyrosine kinase inhibitors and surgical intervention in patients with metastatic or recurrent gastrointestinal stromal tumors: A 14-year, single-center experience

Cancer Med. 2019 Mar;8(3):1034-1043. doi: 10.1002/cam4.1994. Epub 2019 Jan 28.

Abstract

The long-term effects of tyrosine kinase inhibitors (TKIs), including imatinib, and surgical intervention on advanced gastrointestinal stromal tumor (GIST) were evaluated. All 379 patients had metastatic or recurrent GIST and started 400 mg/d imatinib at the Asan Medical Center in periods 1 and 2 [2001-2007 (33.2%) and 2008-2014 (66.8%), respectively]. Men constituted 60.4%; median patient age and tumor size at the initiation of imatinib were 58.6 (14.6-85.5) years and 51 (0-324) mm, respectively, without differences between periods except for older age and less preimatinib surgery in period 2. Response and disease control rates with imatinib in measurable GIST were 63.1% and 94.3%, respectively, without differences between periods. More patients in period 2 underwent surgical resection for TKI-responsive diseases within the first 2 years (24.9%, P = 0.006). With a median follow-up of 6.1 years (2.5-16.0) in survivors, median progression-free survival (PFS) was 5.4 years [95% confidence interval (CI), 4.0-6.9]. Subsequent sunitinib (P = 0.066) and regorafenib (P = 0.003) were more commonly administered in period 2. Median overall survival (OS) was 8.8 years (95% CI, 7.8-9.7). PFS with imatinib (P = 0.002) and OS (P = 0.019) were significantly longer in period 2. Young age, smaller tumor size at the initiation of imatinib, KIT exon 11 mutation, surgical intervention, and period 2 were favorable factors for PFS and OS. Patients with advanced GIST showed better prognosis with the optimal use of imatinib, along with active surgical intervention and more common use of subsequent TKIs in period 2.

Keywords: gastrointestinal stromal tumor; imatinib mesylate; survival.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cancer Survivors
  • Cohort Studies
  • Combined Modality Therapy
  • Female
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / mortality
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / surgery*
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / mortality
  • Gastrointestinal Stromal Tumors / pathology
  • Gastrointestinal Stromal Tumors / surgery*
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases