February 1, 2012 — The US Food and Drug Administration (FDA) has approved the extended use of imatinib (Gleevec, Novartis) in the adjuvant treatment of gastrointestinal stromal tumors (GIST). The product's label has been updated to highlight new data showing that overall survival is significantly increased when the drug is taken for 3 years after surgery, rather than for the standard 1 year.
These data come from a clinical trial presented at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO). As reported at the time by Medscape Medical News, that study involved 400 patients with KIT (CD117)-positive GIST who were — after surgical resection of the tumor — randomized to receive imatinib 400 mg/day for either 1 or 3 years. At the median 5-year follow-up, more patients in the 3-year group than in the 1-year group were still alive (92% vs 82%; hazard ratio [HR], 0.45; P = .019). In addition, there was a significant improvement in 5-year relapse-free survival (65.6% vs 47.9%; HR, 0.46; P < .0001).
These results were highlighted as one of the " major clinical cancer advances of 2011" by ASCO in its end-of-year review.
Imatinib was approved in 2001 for use in the treatment of chronic myelogenous leukemia, and was granted accelerated approval in 2002 for use in advanced or metastatic GIST. This was changed to a regular approval for metastatic GIST in 2008.
In 2008, imatinib was granted subsequent accelerated approval for use as adjuvant treatment in patients who had a potentially curative resection of GIST tumors but who were at high risk for relapse. It is this indication that has now been extended to allow 3 years of treatment after surgery, rather than the standard 1 year.
"The development of [imatinib] over the past decade highlights the need to study drugs after approval to truly characterize their benefits," said Richard Pazdur, MD, director of the FDA's Office of Hematology and Oncology Products.
The US National Comprehensive Cancer Network updated its clinical practice guidelines in August 2011 to recommend a consideration of 3 years of adjuvant therapy with imatinib in patients with high-risk GIST.
However, when the new data were being discussed at the ASCO meeting last year, there was some debate about whether imatinib treatment should be continued for even more than 3 years. Discussant for the paper, Charles D. Blanke, MD, from the University of British Columbia, Vancouver, Canada, said that 3 years of adjuvant imatinib therapy "represents the new gold standard."
"For now, with the overall survival benefit demonstrated with immediate postoperative imatinib, it is no longer acceptable to withhold treatment in the adjuvant setting, hoping to 'catch up' when the patient has recurrent metastatic disease," Dr. Blanke said.
But, he asked: "Should we treat longer than 3 years? Should we treat forever?"
"There are plenty of reasons to think that giving imatinib for a longer period would be better, but that theory remains unproven," he continued.
Of course, economic issues and the number of patients available for clinical trials limit the feasibility of studying this issue further, he noted. In fact, he added, the National Cancer Institute rejected a trial proposal recently designed to compare 5- to 10-year imatinib with lifetime imatinib. "I doubt that they will change their mind," even after the results of this study, he said.
These data come from a clinical trial presented at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO). As reported at the time by Medscape Medical News, that study involved 400 patients with KIT (CD117)-positive GIST who were — after surgical resection of the tumor — randomized to receive imatinib 400 mg/day for either 1 or 3 years. At the median 5-year follow-up, more patients in the 3-year group than in the 1-year group were still alive (92% vs 82%; hazard ratio [HR], 0.45; P = .019). In addition, there was a significant improvement in 5-year relapse-free survival (65.6% vs 47.9%; HR, 0.46; P < .0001).
These results were highlighted as one of the " major clinical cancer advances of 2011" by ASCO in its end-of-year review.
Imatinib was approved in 2001 for use in the treatment of chronic myelogenous leukemia, and was granted accelerated approval in 2002 for use in advanced or metastatic GIST. This was changed to a regular approval for metastatic GIST in 2008.
In 2008, imatinib was granted subsequent accelerated approval for use as adjuvant treatment in patients who had a potentially curative resection of GIST tumors but who were at high risk for relapse. It is this indication that has now been extended to allow 3 years of treatment after surgery, rather than the standard 1 year.
"The development of [imatinib] over the past decade highlights the need to study drugs after approval to truly characterize their benefits," said Richard Pazdur, MD, director of the FDA's Office of Hematology and Oncology Products.
The US National Comprehensive Cancer Network updated its clinical practice guidelines in August 2011 to recommend a consideration of 3 years of adjuvant therapy with imatinib in patients with high-risk GIST.
However, when the new data were being discussed at the ASCO meeting last year, there was some debate about whether imatinib treatment should be continued for even more than 3 years. Discussant for the paper, Charles D. Blanke, MD, from the University of British Columbia, Vancouver, Canada, said that 3 years of adjuvant imatinib therapy "represents the new gold standard."
"For now, with the overall survival benefit demonstrated with immediate postoperative imatinib, it is no longer acceptable to withhold treatment in the adjuvant setting, hoping to 'catch up' when the patient has recurrent metastatic disease," Dr. Blanke said.
But, he asked: "Should we treat longer than 3 years? Should we treat forever?"
"There are plenty of reasons to think that giving imatinib for a longer period would be better, but that theory remains unproven," he continued.
Of course, economic issues and the number of patients available for clinical trials limit the feasibility of studying this issue further, he noted. In fact, he added, the National Cancer Institute rejected a trial proposal recently designed to compare 5- to 10-year imatinib with lifetime imatinib. "I doubt that they will change their mind," even after the results of this study, he said.
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