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10-Year Outcomes With Two Dose Levels of Imatinib in Unresectable or Metastatic GIST

Key Points

  • Among patients with locally advanced unresectable or metastatic GISTs receiving imatinib at 400 or 800 mg/d, estimated 10-year progression-free survival rates were 9.5% vs 9.2%, respectively; 10-year overall survival rates were 19.4% vs 21.5%, respectively.
  • Better performance status, smaller largest lesion size, and KIT exon 11 mutation were associated with better overall survival.

Casali et al have reported 10-year progression-free and overall survival rates among patients with locally advanced unresectable or metastatic gastrointestinal stromal tumors (GISTs) receiving imatinib at 400 or 800 mg/d in the phase III European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group intergroup trial. These findings were reported in the Journal of Clinical Oncology.

Study Details

In the trial, 946 patients with CD117-positive GIST from 56 institutions in 13 countries were randomized between February 2001 and February 2002 to receive imatinib at 400 mg once daily (n = 473) or twice daily (800 mg daily; n = 473). Patients in the 400-mg group were permitted to cross over to 800 mg upon disease progression.

10-Year Outcomes

Median follow-up was 10.9 years. Median progression-free survival was 1.7 years in the 400-mg group vs 2.0 years in the 800-mg group (hazard ratio [HR] = 0.91, P = .18), and median overall survival was 3.9 years vs 3.9 years (HR = 0.93, P = .31). Estimated 10-year progression-free survival rates were 9.5% vs 9.2%; 10-year overall survival rates were 19.4% vs 21.5%. Of the 417 patients in the 400-mg group who experienced disease progression, 196 crossed over to 800 mg after disease progression and 103 continued imatinib off protocol.

On multivariate analysis, younger age (overall P < .01), World Health Organization performance status (0 vs ≥ 1, overall P < .01), smaller size of the largest lesion (HR = 1.03 per 10-mm increase, P < .01), and KIT exon 11 mutation (HRs = 1.87–2.68 for exon 9 mutation, wild-type, and other vs exon 11 mutation; overall P < .01) were significantly associated with probability of surviving beyond 10 years. Additional prognostic factors for survival were no prior chemotherapy (HR = 1.31 for prior chemotherapy, P <.01) and female vs male sex (HR = 0.83, P = .02).

The investigators concluded: “This trial was carried out on a worldwide intergroup basis, at the beginning of the learning curve of the use of imatinib, in a large population of patients with advanced GIST. With a long follow-up, 6% of patients are long-term progression free and 13% are survivors. Among clinical prognostic factors, only performance status, KIT mutation, and size of largest lesion predicted long-term outcome, likely pointing to a lower burden of disease. Genomic and/or immune profiling could help understand long-term survivorship. Addressing secondary resistance remains a therapeutic challenge.”

The study was supported by the European Organisation for Research and Treatment of Cancer Cancer Research Fund.

Paolo G. Casali, MD, of the Istituto Nazionale dei Tumori, Milan, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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