Long-Term Imatinib Therapy Delays GIST Recurrence

Five-year treatment of patients with resected primary gastrointestinal stromal tumor (GIST) with imatinib was not associated with disease recurrence during therapy, and any recurrence that took place happened within 2 years of therapy discontinuation, according to results from a recent clinical trial (JAMA Oncol. 2018 Nov 1. Epub ahead of print).

“[A]djuvant imatinib therapy of any duration appears to delay recurrence of GIST and, in a subset of patients, may improve survival. However, it is unclear whether extending exposure to imatinib beyond 3 years will further delay recurrence by shifting the RFS [recurrence-free survival] curve or biologically impacting the disease to prevent recurrences and decrease the slope of the RFS curve for high-risk patients,” explained lead investigator Chandrajit P. Raut, MD, MSc, Division of Surgical Oncology, Brigham and Women's Hospital, Boston, Massachusetts, and colleagues.

Thus, Dr Raut and colleagues conducted the prospective, multicenter, single-arm, phase 2 Postresection Evaluation of Recurrence-free Survival for Gastrointestinal Stromal Tumors With 5 Years of Adjuvant Imatinib (PERSIST-5) clinical trial to determine the long-term safety, tolerability, and efficacy of adjuvant imatinib used for 5-years in this patient population.

A total of 91 adults with primary GIST from 21 US institutions who underwent a complete resection and had intermediate or high risk of recurrence were included in the study. More than 50% of these patients were men, and the median age was 60 years; median tumor size was 6.5 cm.

The primary and secondary end points were RFS and overall survival (OS), respectively. Dr Raut and colleagues collected patient data from August 5, 2009, through December 20, 2016.

Patients received oral imatinib 400 mg once daily for 5 years or until disease progression or therapy intolerance. A total of 46 (51%) patients completed 5 years of therapy with imatinib; the median duration of treatment was 55.1 months.

The estimated 5-year RFS and OS were 90% and 95%, respectively. Disease recurrence was observed 7 patients—1 had disease recurrence during imatinib therapy, whereas 6 patients had disease recurrence after imatinib discontinuation.

A total of 45 (49%) patients discontinued therapy early out of personal choice (21%) or because of adverse events (16%); 12% stopped therapy for other unspecified reasons. All 91 patients had ³1 adverse events, and 17 (19%) had grade 3 or 4 adverse events. Two patients died, but their deaths were not associated with imatinib therapy or tumor progression.

“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 concluded.

“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 added.—Hina Khaliq