5-Year Adjuvant Imatinib Yields Positive Outcomes, Low Adherence Rates in Patients With Primary GIST

Certain patients with resected primary gastrointestinal stromal tumors can benefit from an extended duration of adjuvant therapy with imatinib, but patient adherence to the therapy long-term remains a challenge, according to results from a recent study by Chandrajit P. Raut, MD, MSc, Division of Surgical Oncology, Brigham and Women's Hospital, Boston, Massachusetts, and colleagues (JAMA Oncol. 2018 Dec 1;4[12]:e184060).

“Three years of adjuvant imatinib mesylate therapy is associated with reduced recurrence rates and improved overall survival in patients with high-risk primary gastrointestinal stromal tumor (GIST) compared with patients who receive 1 year of treatment,” they explained, adding that it is unknown what effect the therapy would have if treatment duration was extended.

Thus, Dr Raut and colleagues conducted a prospective, single-arm, phase 2 clinical trial to determine the 5-year efficacy and tolerability of using adjuvant imatinib in patients with primary GIST.

A total of 91 patients with primary GIST who underwent macroscopically complete resections at 21 institutions were recruited for the study. Of these patients, 48 (53%) were men with a median age of 60 years.

All patients were at intermediate- or high-risk for disease recurrence and received oral imatinib 400 mg once daily for 5 years or until treatment discontinuation due to disease progression or intolerance.

Dr Raut and colleagues collected data between August 5, 2009, and December 20, 2016; the primary end point of the trial was recurrence-free survival (RFS), and the secondary end point was overall survival.

The median tumor size was 6.5 cm, and treatment duration lasted a median of 55.1 months; 46 (51%) patients took imatinib therapy for 5 years.

Findings demonstrated an estimated 5-year RFS of 90% (95% confidence interval [CI], 80%-95%). The rate of overall survival was 95% (95%CI, 86%-99%). A total of 7 patients had disease recurrence—in 1 patient’s case, this happened during treatment with imatinib, whereas the 6 others had disease recurrence after discontinuing the drug. The patient who had disease recurrence during imatinib therapy died, as did 2 other patients, although they died of reasons deemed unrelated to treatment or tumor progression.

Approximately 50% of patients discontinued treatment early because of personal choice (21%), adverse events (16%), or other reasons (12%). All 91 patients in the study experienced at least 1 adverse event; 17 (19%) had adverse events that were grade 3 or 4.

“In our trial, 5 years of adjuvant imatinib therapy was safe and effective at controlling recurrence rates in patients with imatinib-sensitive mutations while receiving therapy following resection of primary GIST. Because of the high early discontinuation rate with prolonged therapy, clinician support of patients receiving imatinib may improve compliance with their adjuvant regimen,” Dr Raut and colleagues said.

“A randomized trial of 3-year therapy vs 5-year therapy of imatinib that is currently under way will help determine whether a longer duration of therapy is superior,” they concluded.—Hina Khaliq