Long-term Imatinib Recommended for Metastatic GIST Even After Complete Resection, French Study Shows

July 1, 2006

Patients with metastatic gastrointestinal stromal tumors (GIST) who are in complete remission after surgical resection remain at high risk for relapse and should continue long-term treatment with imatinib (Gleevec), according to Binh Nguyen Bui, MD, of Institut Bergonie, Bordeaux, France. Dr. Bui reported results of the French Sarcoma Group BFR14 randomized phase III trial at the American Society of Clinical Oncology 42nd Annual Meeting (abstract 9501).

ATLANTA-Patients with metastatic gastrointestinal stromal tumors (GIST) who are in complete remission after surgical resection remain at high risk for relapse and should continue long-term treatment with imatinib (Gleevec), according to Binh Nguyen Bui, MD, of Institut Bergonie, Bordeaux, France. Dr. Bui reported results of the French Sarcoma Group BFR14 randomized phase III trial at the American Society of Clinical Oncology 42nd Annual Meeting (abstract 9501).

Although this trial was described as a study of adjuvant imatinib, session chair George D. Demetri, MD, of Harvard Medical School and Dana-Farber Cancer Institute, pointed out that it was more a study of the benefits of surgery as an adjuvant to imatinib treatment.

The study, supported by Novartis, enrolled 290 patients with metastatic disease; patients had surgery if there was thought to be a possibility of complete resection (R0-R1). All patients were treated with imatinib (400 mg/d), and 239 patients (either complete response to imatinib or R0-R1 resection) were randomized to continuation of imatinib (400 mg/d) until disease progression or discontinuation of imatinib.

Dr. Bui reported 3-year follow-up data for 153 patients, including 99 with initial R0, R1, or Rx (indeterminate) surgery of metastases (surgery group) and 54 without initial surgery or with R2 surgery of metastases (the nonsurgery group). Primary disease was gastric in about 40% of each group. However, only 8 patients (15.4%) in the no-surgery group had small bowel primary disease, compared with 40 (41.2%) in the surgery group.

According to Dr. Bui, the 3-year data show no difference in overall survival between the patients with complete resection and those with residual tumor. There was also no overall survival difference between the nonsurgery patients and those who had R0-R1 resections.

Among the 40% of patients who progressed, Dr. Bui said, there was no difference in progression-free interval between the surgery and nonsurgery groups.

"Subgroup analysis [for overall survival] found that patients with only liver metastases may have some marginal benefit from complete resection before imatinib treatment (P = .056)," Dr. Bui said. In addition, among the gastric primary GIST patients, overall survival was higher in the surgery group, compared with the no-surgery group (P = .044). Dr. Bui noted that the numbers were small in both of these subgroup analyses.

The researchers concluded that these results "justify imatinib treatment of initially resected metastatic GIST as in other metastatic diseases." Dr. Bui noted that optimal duration of imatinib has yet to be determined.