CHICAGO, June 6 -- Imatinib (Gleevec) after curative surgery for gastrointestinal stromal tumors resulted in a 90% recurrence-free survival after two years.
That compared with a 71% two-year recurrence free survival among patients who had curative surgery plus placebo, said surgical oncologist Ronald DeMatteo, M.D., of Memorial Sloan-Kettering Cancer Center in New York, at the American Society of Clinical Oncology meeting here.
"This highly significant result (P<0.001) could prompt re-evaluation of clinical practice recommendations for management of intermediate- and high-risk primary resectable GISTs," said Dr. DeMatteo, principal investigator for the North American Intergroup Phase III Trial ACOSOG V Z 9001.
Action Points
- Explain to interested patients that the GIST patients in this study had to be Kit-positive for eligibility.
- The findings were reported at a poster session at a medical conference and as a published abstract and should be considered preliminary until they appear in a peer-reviewed journal.
Moreover, the difference in outcomes was significant after one year, the researchers found. After 12 months 97% of imatinib patients were disease free and alive, compared with 83% of patients in the placebo group. That difference translated to an 82% reduction in the risk of disease recurrence, he said.
The study enrolled 644 patients who had been diagnosed with GIST and were considered at higher risk for recurrence. Patients were included in the study design if they were determined to have Kit (CD117)-positive GIST.
"Conventional chemotherapy agents have been notoriously ineffective in GIST. This study demonstrated for the first time that targeted molecular therapy reduces the rate of recurrence after complete removal of a primary GIST," Dr. DeMatteo said.
Imatinib therapy was generally well tolerated by most patients in the adjuvant GIST study, with side effects similar to those observed in other GIST clinical trials with imatinib including nausea, diarrhea and edema.
The trial's data safety monitoring committee stopped enrollment in April 2007 because the primary endpoint of increasing recurrence-free survival had been met. Patients in the study who were being treated with placebo were offered one year of imatinib treatment.
The halting of the trial gave ASCO the opportunity to present the first look at the data behind that decision, but the process was so rushed that there was not even enough time to assign an abstract number -- let alone publish an abstract -- for Dr. DeMatteo's presentation.
In a statement, Novartis said it planned to seek FDA approval for use of imatinib as adjuvant therapy in respectable GIST patients and expected to submit a formal application by early 2008. Imatinib is approved for the treatment of patients with Kit (CD117)-positive unresectable and/or metastatic malignant GIST.
Estimates of the occurrence rate of GIST in the United States vary, but experts believe there are between 1,500 and 6,000 new cases each year. Although surgery cures some patients with GIST, the recurrence rate is high.
| Novartis supplied imatinib for use in the study, and also provided partial funding under a Cooperative Research and Development Agreement with National Cancer Institute to support the clinical development of imatinib. Dr. DeMatteo said he had received financial support from Novartis. |
Primary Source
American Society of Clinical Oncology
Source Reference: Ronald DeMatteo, "Adjuvant Imatinib Mesylate increases recurrence free survival in patients with completely resected primary gastrointestinal stromal tumors: North American Intergroup Phase III Trial ACOSOG V Z 9001" 2007 ASCO Annual Meeting Pocket program, P. 443.