Imatinib escalation or sunitinib treatment after first-line imatinib in metastatic gastrointestinal stromal tumor patients

Anticancer Res. 2014 Sep;34(9):5029-36.

Abstract

Aim: Imatinib mesylate (IM) is effective in metastatic gastrointestinal stromal tumor (GIST) patients; however, disease progression eventually occurs due to IM resistance or intolerance. Treatment options include IM escalation or a direct shift to sunitinib, but comparison of these strategies is required.

Patients and methods: This study included 91 out of 214 metastatic GIST patients treated with IM, who experienced progression or intolerance between August 2001 and December 2012 at the Chang Gung Memorial Hospital. Treatment efficacy and safety profiles were retrospectively compared between groups of patients who either received escalated IM or were directly switched to sunitinib.

Results: There were no significant differences in age, gender, second-line treatment causes or gene mutations in the IM escalation group (N=63) versus the sunitinib group (N=28). The 2 groups had similar progression-free survival (PFS, p=0.316) and overall survival (OS, p=0.599). Patients without primary KIT exon 9 mutations and who treated with sunitinib had significantly better PFS (14.3 vs. 6.2 months, p=0.037) and a trend toward better OS (not reached vs. 16.4 months, p=0.161) compared to the IM-escalation group. Patients in both groups with responses and stable disease (SD), and IM escalation patients who underwent surgery and who had KIT exon 9 mutations, had favorable PFS. The most common non-hematological adverse events were edema in the IM escalation group and hand-foot syndrome and hypertension in the sunitinib group.

Conclusion: Comparable results were achieved by IM escalation and sunitinib treatment. Physicians should consider kinase mutations and specific adverse effects when choosing between these treatments.

Keywords: Gastrointestinal stromal tumor; imatinib mesylate; second-line therapy; sunitinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Benzamides / administration & dosage
  • Benzamides / adverse effects
  • Benzamides / therapeutic use*
  • Drug Substitution
  • Female
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / mortality
  • Gastrointestinal Neoplasms / pathology*
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / mortality
  • Gastrointestinal Stromal Tumors / pathology*
  • Humans
  • Imatinib Mesylate
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Prognosis
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Retreatment
  • Sunitinib
  • Treatment Outcome
  • Young Adult

Substances

  • Benzamides
  • Indoles
  • Piperazines
  • Pyrimidines
  • Pyrroles
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Sunitinib