Clinical trial data showing a significant increase in survival when imatinib is used for 3 years as adjuvant therapy after resection of Kit-positive gastrointestinal stromal tumors has been added to the drug’s label.
The change "highlights an increase in overall patient survival when the drug is taken for 36 months rather than the standard 12 months of treatment," the Food and Drug Administration said in a Jan. 31 statement.
The agency also announced the granting of "regular" approval to imatinib (Gleevec) as adjuvant treatment for adults "following gross resection of Kit (CD117) positive" gastrointestinal stromal tumors (GIST). This indication had received an accelerated approval in 2008; accelerated approvals are granted to provide earlier access to a drug while confirmatory trials required for full approval are under way.
Imatinib, an oral tyrosine kinase inhibitor, was initially approved by the FDA in 2001 to treat patients with advanced Philadelphia chromosome–positive chronic myeloid leukemia. It received an accelerated approval for the treatment of advanced or metastatic GIST in 2002; this was converted to a full approval in 2008 based on confirmatory trials.
"The development of Gleevec over the past decade highlights the need to further study drugs after approval to truly characterize their benefits," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the agency’s statement.
"Although originally approved in the metastatic disease setting, this subsequent trial has demonstrated that longer use of Gleevec can prolong patient’s lives in earlier disease settings," he added.
The data added to the label come from a large, international, randomized open-label phase III study of patients with more than a 50% estimated risk of recurrence of GIST. The overall survival rate at 5 years was 92% among patients treated for 36 months with imatinib, compared with 82% in those treated for 12 months, according to the FDA.
The longer overall survival among those who received 36 months of imatinib treatment after surgery represents a 55% reduced risk of death, according to a statement from Novartis Pharmaceuticals Corp., which markets Gleevec.
Recurrence-free survival also was longer among those treated for 36 months, with a 54% reduced risk of risk of recurrence compared with the 12-month schedule, Novartis said.
Dr. Heikki Joensuu of Helsinki University Central Hospital in Finland presented the trial results in a plenary session at the annual meeting of the American Society of Clinical Oncology in June 2011. Click here to see a full report of his presentation and a video interview with Dr. Joensuu on the findings.
In August 2011, the National Comprehensive Cancer Network recommended consideration of at least 3 years of adjuvant treatment with imatinib in patients with high-risk GIST, according to Novartis.
The most common side effects associated with treatment with imatinib include edema, nausea, vomiting, muscle cramps, bone or muscle pain, diarrhea, rash, fatigue, and abdominal pain, according to the FDA.
It identified the recommended dose of imatinib for adjuvant treatment as 400 mg/day administered with meals daily for 3 years but noted that the optimal duration of treatment is not known.