FDA approves imatinib mesylate tablets for GIST

Issue: February 25, 2012

The FDA today approved imatinib mesylate tablets for the adjuvant treatment of adult patients after complete gross resection of CD117-positive gastrointestinal stromal tumors.

Imatinib (Gleevec, Novartis Pharmaceuticals) was originally granted accelerated approval in December 2008 for adjuvant use in patients with gastrointestinal stromal tumors (GIST) who had undergone potentially curative resection of GIST tumors but were at increased risk for a recurrence. Imatinib also has received revised labeling to include the results of a randomized trial demonstrating that recurrence-free survival and OS were improved by continuing with adjuvant imatinib treatment for 36 months.

According to the results of an adjuvant, multicenter, open-label, phase 3 trial, 397 patients were randomly allocated to receive 12 (n=199) or 36 months (n=198) of imatinib treatment, in doses of 400 mg orally daily. Patient eligibility for inclusion in this study adhered to the following criteria: tumor diameter of more than 5 cm and mitotic count of more than 5/50 high power fields; tumor diameter of more than 10 cm and any mitotic count; tumor of any size with mitotic count of more than 10/50 high power fields; or tumors that had ruptured into the peritoneal cavity.

In the study, recurrence-free survival was identified as the time from the beginning of treatment to the date of recurrence and/or death from any cause — median follow-up for patients without a recurrence-free survival event was 42 months. From the study results, 36 months of imatinib treatment was observed to significantly prolong recurrence-free survival compared with 12 months (HR=0.46; 95% CI, 0.32-0.65).

Similar beneficial results also were observed in the OS results of the study. With a median follow-up of 49 months for OS, the study results showed that there were 25 (13%) deaths in the 12-month treatment arm compared with 12 (6%) deaths in the 36-month treatment arm (HR=0.45; 95% CI, 0.22-0.89).

“The development of Gleevec over the past decade highlights the need to further study drugs after approval to truly characterize their benefits,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “Although originally approved in the metastatic disease setting, this subsequent trial has demonstrated that longer use of Gleevec can prolong patients’ lives in earlier disease settings.”

Adverse reactions from imatinib treatment were observed in 8% of the 12-month treatment arm (n=15) and 14% in the 36-month treatment arm (n=27), including edema, nausea, diarrhea, rash, fatigue, vomiting, muscle cramps, bone or muscle pain, and abdominal pain.

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