The FDA has approved a new indication for Gleevec (imatinib mesylate, Novartis) for use in certain adult patients following surgical removal of KIT (CD117)-positive gastrointestinal stromal tumors (GIST). The new labeling recommends 36 months of treatment with Gleevec after surgery in adult patients with KIT-positive GIST who meet the risk for recurrence inclusion criteria of the pivotal trial. The 36-month treatment regimen was shown to improve recurrence-free survival (RFS) and overall survival (OS) in patients with KIT-positive GIST compared with 12 months of treatment.
The new approval is based on data from an international, multicenter, open-label Phase III clinical trial (SSG XVIII) conducted by the Scandinavian Sarcoma Group and the Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie. The primary end point of the study was to compare, within the first five years, RFS in patients with a greater than 50% estimated risk for GIST recurrence following diagnosis and treatment with adjuvant Gleevec for either 12 or 36 months. Results of the study revealed that RFS was longer for patients assigned to receive 36 months of Gleevec after surgery compared with those who received 12 months of treatment, for a 54% reduction in risk for GIST recurrence (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.32-0.65;P<0.0001). Additionally, OS was longer in the 36-month treatment group, which resulted in a 55% reduction in the risk for death (HR, 0.45; 95% CI, 0.22-0.89;P=0.0187). Gleevec manufacturer Novartis provided funding for the study.
Gleevec was originally granted accelerated approval for the treatment of advanced or metastatic GIST in 2002. In 2008, Gleevec was granted accelerated approval for adjuvant use for the treatment of patients with GIST who had had potentially curative resection (surgical removal) of GIST, but who had an increased risk for recurrence. Approval for the metastatic GIST indication also was granted in 2008.
“The development of Gleevec over the past decade highlights the need to further study drugs after approval to truly characterize their benefits,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, 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.”
GIST is a rare form of cancer that originates in cells found in the wall of the gastrointestinal tract. These cells, known as interstitial cells of Cajal, are part of the autonomic nervous system, which regulates body processes such as food digestion. The major cause of GIST is an abnormal form of the protein KIT, which causes cells to grow uncontrollably and become cancerous. Gleevec is indicated for the treatment of patients with KIT-positive GIST that are cancerous, cannot be surgically removed and/or have spread to other parts of the body. The drug also is approved for use after surgery in patients who have had KIT-positive GIST completely removed. Additionally, Gleevec is approved for the treatment of other cancers; it was first approved by the FDA in 2001 to treat patients with advanced Philadelphia chromosome-positive chronic myeloid leukemia, a blood and bone marrow disease linked to a genetic abnormality.
For more information about Gleevec, visit www.gleevec.com.
—Based on press releases from the FDA and Novartis Pharmaceuticals