PERSIST-5: 5-Year Adjuvant Imatinib in Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor
In the phase II PERSIST-5 study reported in JAMA Oncology, Raut et al found that 5 years of adjuvant imatinib therapy was associated with little risk of recurrence in patients with resected intermediate- or high-risk primary gastrointestinal stromal tumor (GIST). As noted by the investigators, 3 years of adjuvant imatinib has been shown to reduce recurrence and improved survival vs 1 year in this setting.
The study included 91 adult patients with primary GIST at 21 U.S. sites who underwent complete resection and were at intermediate or high risk of recurrence, defined as primary GIST at any site measuring ≥ 2 cm with ≥ 5 mitoses per 50 high-power field or nongastric primary GIST measuring ≥ 5 cm. Patients were to receive imatinib at 400 mg once daily for 5 years or until disease progression or intolerance.
Patients had a median age of 60 years, 53% were men, and median tumor size was 6.5 cm. The current report reflects data collected from August 2009 through December 2016.
Treatment Outcomes
Median duration of treatment was 55.1 months (range = 0.5–60.6 months). In total, 46 patients (51%) completed 5 years of imatinib therapy. Among the remaining 45 patients, the most common causes of early discontinuation of treatment were patient choice (21%) and adverse events (16%). Estimated 5-year recurrence-free survival was 90% (95% confidence interval [CI] = 80%–95%) and 5-year overall survival was 95%.
Among the 91 patients, recurrence was observed in 7 patients (8%). One patient, with the imatinib-insensitive PDGFRA D842V mutation, had recurrence during imatinib treatment and was the only patient to die from progressive disease. Recurrence in the other 6 patients was observed at 7.4 to 23.1 months after patients had stopped treatment; 5 of these patients harbored imatinib-insensitive mutations at baseline. Recurrence, after discontinuation of treatment, was observed in only 1 of 57 patients with an imatinib-sensitive (KIT exon 11) mutation.
Adverse Events
The most common adverse events of any grade considered related to study treatment were nausea (62%), diarrhea (50%), fatigue (37%), periorbital edema (33%), and muscle spasm (32%). Grade 3 or 4 adverse events related to study treatment occurred in 19%. Two additional deaths occurred during the study, with neither related to progression or study treatment.
The investigators concluded, “In this first adjuvant trial, to our knowledge, of patients with resected primary GIST who received 5 years of imatinib therapy, no patient with imatinib-sensitive mutations had disease recur during therapy. For patients in whom disease recurred, recurrence was within 2 years of discontinuation of imatinib therapy. Approximately half of the patients discontinued treatment early, most commonly because of patient choice, thus emphasizing the importance of close clinical monitoring to continue imatinib treatment for patients at appropriate risk.”
This study was sponsored by Novartis Pharmaceuticals Corporation.
Chandrajit P. Raut, MD, of the Division of Surgical Oncology, Brigham and Women's Hospital, is the corresponding author for the JAMA Oncology article.
Disclosure: See study authors’ full disclosures at jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
