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Original Investigation
December 13, 2018

Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients With Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor: The PERSIST-5 Clinical Trial

Author Affiliations
  • 1Division of Surgical Oncology, Brigham and Women's Hospital, Boston, Massachusetts
  • 2Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 3Harvard Medical School, Boston, Massachusetts
  • 4Department of Surgery, Roger Williams Medical Center, Boston University School of Medicine, Providence, Rhode Island
  • 5Division of Medical Oncology and Hematology, Department of Medicine, Monter Cancer Center, Northwell Health, Lake Success, New York
  • 6Cold Spring Harbor Laboratory, Cold Spring Harbor, New York
  • 7Department of Sarcoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston
  • 8Division of Medical Oncology, Department of Medicine, University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Florida
  • 9Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
  • 10Department of Surgery, University of Pennsylvania, Philadelphia
JAMA Oncol. 2018;4(12):e184060. doi:10.1001/jamaoncol.2018.4060
Key Points

Question  What is the tolerability and efficacy of 5 years of adjuvant imatinib mesylate therapy in patients with resected primary gastrointestinal stromal tumor?

Findings  In this phase 2 study of 91 adults, no patient with resected imatinib-sensitive primary gastrointestinal stromal tumor who received 5 years of adjuvant therapy had disease recur while receiving imatinib. However, rates of early discontinuation of imatinib were high (49%).

Meaning  Longer-duration adjuvant imatinib may be efficacious in appropriately selected patients with resected primary gastrointestinal stromal tumor, but adherence to the planned course of therapy may be challenging despite its benefits.


Importance  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. The impact of a longer duration of therapy is unknown.

Objective  To determine whether adjuvant treatment for primary GIST with imatinib for 5 years is tolerable and efficacious.

Design, Setting, and Participants  This prospective, single-arm, phase 2 clinical trial (Postresection Evaluation of Recurrence-free Survival for Gastrointestinal Stromal Tumors With 5 Years of Adjuvant Imatinib [PERSIST-5]) included adult patients with primary GIST (expressing KIT) at 21 US institutions who underwent a macroscopically complete resection and were at intermediate or high risk of recurrence, defined as primary GIST at any site measuring 2 cm or larger with 5 or more mitoses per 50 high-power field or nongastric primary GIST measuring 5 cm or larger. Data were collected from August 5, 2009, through December 20, 2016.

Interventions  Imatinib, 400 mg once daily, orally for 5 years or until discontinuation of therapy because of progression or intolerance.

Main Outcomes and Measures  The primary end point was recurrence-free survival (RFS). The secondary end point was overall survival.

Results  Of the 91 patients enrolled, 48 (53%) were men with a median age of 60 years (range, 30-90 years). Median tumor size was 6.5 cm (range, 2.3-30.0 cm). Median treatment duration was 55.1 months (range, 0.5-60.6 months); 46 patients (51%) completed 5 years of imatinib therapy. Estimated 5-year RFS was 90% (95% CI, 80%-95%), and overall survival was 95% (95% CI, 86%-99%). Recurrence was noted in 7 patients: 1 had disease recur while receiving imatinib (PDGFRA D842V mutation) and died; 6 had disease recur after discontinuation of imatinib therapy. Two additional deaths were unrelated to treatment or tumor progression. Forty-five patients (49%) stopped treatment early because of patient choice (10 [21%]), adverse events (15 [16%]), or other (11 [12%]). All 91 patients experienced at least 1 adverse event, and 17 (19%) experienced grade 3 or 4 adverse events.

Conclusions and Relevance  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.

Trial Registration  ClinicalTrials.gov identifier: NCT00867113