No better survival with high-dose imatinib for advanced GI stromal tumors

NEW YORK (Reuters Health) - In patients with advanced gastrointestinal stromal tumors, the maximum feasible dose of imatinib produces a small increase in progression-free survival but no improvement in overall survival.

And even the small advantage in progression-free survival was essentially limited to patients with KIT exon 9 mutations, according to researchers.

Their findings, from a meta-analysis of two large trials in patients with unresectable or metastatic disease, appeared online February 1 in the Journal of Clinical Oncology.

"The most interesting aspect of our work was to investigate whether it was beneficial for patients harboring a KIT exon 9 mutation (those with the worst prognosis) to be treated with the high dose up front," Dr. Martine Van Glabbeke of the European Organization for the Research and Treatment of Cancer, which is based in Brussels, told Reuters Health by e-mail.

Although the analysis showed "a clear advantage in terms of progression-free survival ... the corresponding improvement in overall survival was not statistically significant, so we cannot definitely recommend this therapeutic option for those patients, and leave the decision to the treating physician," she noted.

In the two studies in the meta-analysis -- one Canadian/American and the other European/Australian -- selection criteria, treatment protocol, and other core elements were intentionally identical. A total of 1,640 patients received 400 mg of imatinib either once a day (standard dose) or twice a day (high dose). The median follow-up time was 45 months.

The median time to disease progression or death in the high-dose group was 1.95 years versus 1.58 years in the standard-dose group. Overall survival was 4.05 years with the high-dose and 4.08 with the standard-dose.

The presence of the KIT exon 9 mutation was the only factor that predicted better progression-free survival with the high-dose regimen. Even this group, however, had no advantage in terms of overall survival.

"As toxicity of the drug is clearly dose dependent, 400 mg should remain the standard starting dose," the research team concludes. "The only exception may be patients who harbor KIT exon 9 mutations, for whom high-dose therapy would potentially delay the first occurrence of disease progression."

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