March 29, 2012 — Three years of imatinib (Gleevec, Novartis) treatment should now be the standard of care for adjuvant therapy of gastrointestinal stromal tumor (GIST) in patients at high risk for recurrence, say experts.
The study showing superior outcomes after 3 years of imatinib compared with 1 year of imatinib is now publishedin the March 28 issue of JAMA.
This phase 3 trial involving 400 patients was conducted by Heikki Joensuu, MD, from Helsinki University Central Hospital, Finland, and colleagues. Patients who had undergone surgery for GIST and were considered to be at high risk for recurrence were prescribed imatinib, 400 mg/d, but were randomly assigned to take the drug for 3 years or for 1 year.
The results showed that the 3-year schedule significantly improved both relapse-free survival and overall survival when compared with 1 year of therapy. At 5 years' follow-up, 66% of the 3-year group vs 48% of the 1-year group (P < .001) were free of relapse and 92% vs 82% (P = .02) were still alive.
This study has established 3 years of imatinib, 400 mg/d, as the new standard of care for postoperative treatment of patients with resected high-risk GIST, comments Charles D. Blanke, MD, from the University of British Columbia, Vancouver, Canada, in an accompanying editorial.
This study was presented at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) and was listed as a "major clinical cancer advance" of 2011 by ASCO in its year-end review.
After the presentation of these results in June 2011 at the ASCO meeting, the 3-year administration schedule "immediately became preferred therapy in much of North America, Europe, and Asia," Dr. Blanke comments.
Earlier this year, the 3-year administration schedule was approved by European authorities and was alsohighlighted by the US Food and Drug Administration, although the agency also added that the "optimal duration of treatment is unknown," Dr. Blanke notes.
Dr. Blanke also acted as discussant for the study at the 2011 ASCO meeting, where he 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 at that time.
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 said at the meeting.
Continuing Therapy Indefinitely?
Now, in the editorial, Dr. Blanke adds, "some clinicians will choose to use imatinib for a longer period, perhaps choosing to treatment their patients indefinitely."
However, one point to consider is the possibility of a cumulative toxicity from prolonged administration, he notes. Although all patients taking imatinib in the study conducted by Dr. Joensuu and colleagues experienced mild toxicities, significantly more of the patients in the 3-year treatment group had high-grade adverse effects, he points out.
In addition, twice as many patients receiving longer therapy dropped out from the study (25.6% in the 3-year group vs 12.6% in the 1-year group) for reasons other than GIST recurrence.
Dr. Blanke speculates as to the reasons for this. "Were even low-grade toxicities difficult to endure for such a long period of time? Can this be attributed to unwillingness of asymptomatic patients to be adherent with a daily pill?"
Further study of these factors is needed, he suggests, to improve "adherence to expensive therapies that could last for decades."
The study was funded by Novartis, manufacturer of imatinib. Dr. Joensuu reports that his institution has received funding from Novartis, and several coauthors report having received honoraria from Novartis. Dr. Blanke reported that his institution has receiving consulting fees from Novartis and Pfizer and that he has received support for travel from Novartis.
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