Long-term imatinib helpful after GI stromal tumor resection

Last Updated: 2018-11-09

By David Douglas

NEW YORK (Reuters Health) - Five years of adjuvant therapy with the tyrosine kinase inhibitor imatinib mesylate (Gleevec, Novartis) appears to be of benefit following macroscopically complete intra-abdominal resection of primary gastrointestinal stromal tumor (GIST), according to a company-funded study.

In a November 1 online paper in JAMA Oncology, Dr. Chandrajit P. Raut of Brigham and Women's Hospital, Boston, and colleagues note that three years of such therapy was previously shown to be superior to treatment for one year.

In the current study, the team sought to investigate the impact of further extended adjuvant therapy in 91 patients deemed to be at moderate or high risk of occurrence. Their median treatment duration was 55 months. Altogether 46 participants (51%) completed five years of imatinib therapy. Estimated recurrence-free survival was 90% and overall survival was 95%.

As Dr. Raut pointed out by email, "There were two key findings. First, for patients whose tumors harbored mutations known to be sensitive to imatinib, there were no recurrences while imatinib therapy was continued. The only patient who recurred while taking imatinib had a mutation which we now know is insensitive to imatinib. The six other patients who recurred in this study did so after stopping imatinib therapy."

"This," he continued, "stresses the importance of both checking GIST mutation profile and continuing imatinib therapy when feasible. The drug safety profile for the extended treatment period was no different than that reported for imatinib in this disease previously."

"The second key finding," Dr. Raut said, "was that 49 percent of patients stopped the drug early, before completing five years of therapy. This shows the challenge of administering adjuvant therapy in someone who ostensibly has undergone a potentially curative operation for primary GIST, despite the growing body of evidence demonstrating the long-term advantages of continued drug therapy."

"Based on these results," he noted, "we would support sustained adjuvant imatinib therapy in appropriately selected patients with primary GIST with sensitive mutations, and we would emphasize the importance of continued close follow-up and support by the treating oncologist to try to keep patients on therapy."

Dr. Raut concluded by noting that a European trial currently underway "will build on this study to further identify appropriate duration of therapy."

Commenting by email, Dr. Scott M. Schuetze, Medical Director of Oncology at the University of Michigan, Ann Arbor, told Reuters Health, "The findings in this non-randomized clinical trial do not prove that 5 years is better than 3 years of imatinib therapy after removal of a high-risk GIST; however, the 90% 5-year relapse-free survival rate is encouraging."

Dr. Schuetze, who was not involved in the study, noted, "There was a high rate of early discontinuation of imatinib therapy for reasons other than disease progression which highlights potential problems (including adverse effects, annoyance, inconvenience of frequent follow-up, and financial burden) of long-term adjuvant drug therapy after surgery without clear demonstration of impact on overall survival."

"The authors," he concluded, "appropriately discuss that in the current era of GIST treatment, molecular sub-classification of GIST should be performed to identify imatinib-sensitive sub-type prior to embarking on prolonged adjuvant imatinib therapy."

Novartis Pharmaceuticals Corporation funded the study and two of the authors are employees of the company.

SOURCE: http://bit.ly/2DtU4LO

JAMA Oncol 2018.