Clinical outcomes of patients with advanced gastrointestinal stromal tumors: safety and efficacy in a worldwide treatment-use trial of sunitinib

Cancer. 2015 May 1;121(9):1405-13. doi: 10.1002/cncr.29220. Epub 2015 Jan 13.

Abstract

Background: The objectives of this study were to provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain it and to collect broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. (ClinicalTrials.gov identifier NCT00094029).

Methods: Imatinib-resistant/intolerant patients with advanced GIST received sunitinib on an initial dosing schedule of 50 mg daily in 6-week cycles (4 weeks on treatment, 2 weeks off treatment). Tumor assessment frequency was according to local practice, and response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS) and safety were assessed regularly. Post hoc analyses evaluated different patterns of treatment management.

Results: At final data cutoff, 1124 patients comprised the intent-to-treat population, and 15% of these patients had a baseline Eastern Cooperative Oncology Group performance status ≥2. The median treatment duration was 7.0 months. The median time to tumor progression was 8.3 months (95% confidence interval [CI], 8.0-9.4 months), the median OS was 16.6 months (95% CI, 14.9-18.0 months), and 36% of patients were alive at the time of analysis. Patients for whom the initial dosing schedule was modified exhibited longer median OS (23.5 months) than those who were treated strictly according to the initial dosing schedule (11.1 months). The most common treatment-related grade 3 and 4 adverse events were hand-foot syndrome (11%), fatigue (9%), neutropenia (8%), hypertension (7%), and thrombocytopenia (6%). Treatment-related adverse events associated with cardiac function (eg, congestive heart failure and myocardial infarction) were reported at frequencies of ≤1% each.

Conclusions: This treatment-use study confirms the long-term safety and efficacy of sunitinib in a large international population of patients with advanced GIST after imatinib failure.

Keywords: efficacy; gastrointestinal stromal tumor; long-term safety; sunitinib; treatment-use trial; worldwide.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Child
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Fatigue / chemically induced
  • Female
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / mortality
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / mortality
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Sarcoma / drug therapy
  • Sarcoma / mortality
  • Sunitinib
  • Treatment Outcome
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Indoles
  • Pyrroles
  • Sunitinib

Associated data

  • ClinicalTrials.gov/NCT00094029