Long-Term Results From a Randomized Phase II Trial of Standard- Versus Higher-Dose Imatinib Mesylate for Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing <i>KIT</i>

TLDR

Long‑term outcomes for advanced GIST patients treated with imatinib mesylate are unclear, despite earlier trials showing high response rates at 400 and 600 mg/d. The study aimed to assess long‑term survival, failure patterns, and prognostic factors—including KIT mutation status—in patients with advanced GIST treated with imatinib 400 or 600 mg/d. Prospectively collected data on KIT mutations, tumor burden, and other factors were analyzed from 147 patients (73 at 400 mg/d, 74 at 600 mg/d) followed for a median of 63 months. Survival, progression‑free survival, and response rates were essentially identical between doses, with a median overall survival of 57 months; 28 % remained on therapy long‑term, and female sex, exon 11 mutations, and normal albumin and neutrophil counts independently predicted better survival, with almost half of patients living beyond five years regardless of starting dose.

Abstract

The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status.Patients with advanced GIST were enrolled onto an open-label, multicenter trial and were randomly assigned (1:1) to receive imatinib 400 versus 600 mg/d. Data were prospectively collected on KIT mutational status, total tumor area, and other potential prognostic factors. Patients were followed for a median of 63 months.One hundred forty-seven patients were enrolled: 73 were in arm A (imatinib 400 mg/d), and 74 were in arm B (imatinib 600 mg/d). Response rates, median progression-free survival, and median overall survival were essentially identical on both arms, and median survival was 57 months for all patients. Forty-one patients overall (28%) remained on the drug long-term. Female sex, the presence of an exon 11 mutation, and normal albumin and neutrophil levels were independently associated with better survival.Nearly 50% of patients with advanced GIST who were treated with imatinib mesylate survived for more than 5 years, regardless of a 400 or 600 mg/d starting dose.