Three years of imatinib following surgery for KIT-positive gastrointestinal stromal tumor conferred longer recurrence-free survival and OS compared with 12 months of treatment, according to the results of a phase 3 international study.
“Because GIST recurrence is frequent after discontinuation of adjuvant imatinib, studies that evaluate still longer treatments are warranted,” the researchers concluded.
Researchers compared 12 months and 36 months of adjuvant imatinib 400 mg in 200 patients with KIT-positive GIST removed at surgery. Patients were enrolled between February 2004 and September 2008 at 24 hospitals in Finland, Germany, Norway and Sweden. The median follow-up was 54 months.
Patients assigned to 36 months of imatinib had significantly longer recurrence-free survival (HR=0.46; 95% CI, 0.32-0.65) compared with patients assigned to imatinib for 12 months (65.6% vs. 47.9%). In addition, although based on only a small number of deaths, those patients assigned to longer imatinib treatment also had longer OS (HR=0.45; 95% CI, 0.22-0.89). Five-year survival for patients assigned to 36 months of imatinib was 92%, compared with 81.7% among patients assigned 12 months.
In an accompanying editorial, Charles D. Blanke, MD, chief of medical oncology at the University of British Columbia and vice president of the British Columbia Cancer Agency, noted that the FDA recently granted regular approval for adjuvant use of imatinib in adults after resection of KIT-positive GISTs. The results of this trial established 3 years of 400 mg of imatinib per day as the new standard of care for postoperative treatment of patients with resected high-risk GISTs, Blanke added.
“Some clinicians will use imatinib for a longer period, perhaps choosing to treat patients indefinitely. Investigators and clinicians alike will increasingly face the question of best postoperative duration of treatment with cytostatic, biologic targeted agents. However, correlative science provides little guidance,” Blanke wrote. “Laboratory biomarker studies may eventually provide information about which patients are unlikely to have recurrence, and thus are not capable of benefiting from any adjuvant therapy, but questions about curability or duration will not be answered by preclinical trials. As pathway-driven adjuvant therapy becomes more prolonged, increasing patients’ tolerance of even low-grade toxicities will be critical to improve their adherence to expensive treatments that could last for decades.”