FDA Grants Regular Approval for Imatinib Mesylate Tablets
Tuesday, January 31, 2012
The U.S. Food and Drug Administration (FDA) granted regular approval for imatinib mesylate tablets (Gleevec®, Novartis Pharmaceuticals) for the adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive Gastrointestinal Stromal Tumors (GIST). Accelerated approval for this indication was granted in December 2008. Labeling is also revised to include the results of a randomized trial demonstrating that recurrence-free survival (RFS) and overall survival (OS) were improved by continuing adjuvant imatinib therapy to 36 months.
An adjuvant, multicenter, open label, phase 3 trial randomly allocated patients to receive either 12 or 36 months of imatinib treatment. Patients received imatinib, 400 mg orally daily, in both treatment duration arms.
Eligible patients had one of the following criteria: tumor diameter >5 cm and mitotic count >5/50 high power fields (HPF), or tumor diameter >10 cm and any mitotic count, or tumor of any size with mitotic count >10/50 HPF, or tumors that ruptured into the peritoneal cavity. There were 199 patients on the 12-month arm and 198 patients on the 36-month arm. The median age of patients was 61 years (range, 22-84 years).
RFS was defined as the time from date of randomization to the date of recurrence or death from any cause. The median follow-up for patients without a RFS event was 42 months. There were 84 (42%) RFS events in the 12-month treatment arm and 50 (25%) RFS events in the 36-month treatment arm. Thirty-six months of imatinib treatment significantly prolonged RFS compared to 12 months [HR=0.46, (95% CI: 0.32, 0.65), p<0.0001].
The median follow-up for OS in patients still alive was 48 months. There were 25 (13%) deaths in the 12-month treatment arm and 12 (6%) deaths in the 36-month treatment arm. Thirty-six months of imatinib treatment significantly prolonged OS compared to 12 months [HR=0.45, (95% CI: 0.22, 0.89), p=0.0187].
Discontinuation of imatinib therapy due to adverse reactions occurred in 15 patients (8%) and 27 patients (14%) of the 12- and 36-month treatment arms, respectively. The most common adverse reactions, as noted in this and previous imatinib trials, were swelling (edema), nausea, vomiting, muscle cramps, bone or muscle pain, diarrhea, rash, fatigue, and abdominal pain.
Imatinib received accelerated approval for patients with Kit (CD117) positive unresectable and/or metastatic GIST in February 2002. This indication subsequently received regular approval in September 2008.
The recommended dose of imatinib for adjuvant treatment is 400 mg/day administered with meals daily for three years. The optimal duration of treatment is not known.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021588s035lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).