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 KIT.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Blanke
Charles D
CD
Oregon Health and Science University Cancer Center and Portland Veterans Affairs Hospital, Portland, OR, USA. blankec@ohsu.edu
Demetri
George D
GD
von Mehren
Margaret
M
Heinrich
Michael C
MC
Eisenberg
Burton
B
Fletcher
Jonathan A
JA
Corless
Christopher L
CL
Fletcher
Christopher D M
CD
Roberts
Peter J
PJ
Heinz
Daniela
D
Wehre
Elisabeth
E
Nikolova
Zariana
Z
Joensuu
Heikki
H
D000368:Aged; D000418:Albumins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D006801:Humans; D000068877:Imatinib Mesylate; D007958:Leukocyte Count; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D009504:Neutrophils / Q000166:cytology; D010879:Piperazines / Q000008:administration & dosage*; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate
D000418:Albumins; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha