Survival Outcomes Associated With 3 Years vs 1 Year of Adjuvant Imatinib for Patients With High-Risk Gastrointestinal Stromal Tumors: An Analysis of a Randomized Clinical Trial After 10-Year Follow-up

Abstract

Importance: Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor (GIST), but its influence on overall survival (OS) has remained uncertain.

Objective: To evaluate the effect of adjuvant imatinib on OS of patients who have a high estimated risk for GIST recurrence after macroscopically complete surgery.

Design, setting, and participants: In this open-label, randomized (1:1), multicenter phase 3 clinical trial conducted in Finland, Germany, Norway, and Sweden, 400 patients who had undergone macroscopically complete surgery for GIST with a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria were enrolled between February 2004 and September 2008. Data for this follow-up analysis were analyzed from September to November, 2019.

Interventions: Imatinib 400 mg/d administered orally for either 12 months or 36 months after surgery.

Main outcomes and measures: The primary end point was RFS; the secondary objectives included OS and treatment safety.

Results: The intention-to-treat cohort consisted of 397 patients (12-month group, 199; 36-month group, 198; 201 men and 196 women; median [IQR] age, 62 (51-69) years and 60 (51-67) years, during a median follow-up time of 119 months after the date of randomization, 194 RFS events and 96 OS events were recorded in the intention-to-treat population. Five-year and 10-year RFS was 71.4% and 52.5%, respectively, in the 36-month group and 53.0% and 41.8% in the 12-month group (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87; P = .003). In the 36-month group, 5-year OS and 10-year OS rates were 92.0% and 79.0%, respectively, and in the 12-month group 85.5% and 65.3% (HR, 0.55; 95% CI, 0.37-0.83; P = .004). The results were similar in the efficacy population, from which 15 patients who did not have GIST in central pathology review and 24 patients who had intra-abdominal metastases removed at surgery were excluded (36-month group, 10-year OS 81.6%; 12-month group, 66.8%; HR, 0.50; 95% CI, 0.32-0.80; P = .003). No new safety signals were detected.

Conclusions and relevance: Three years of adjuvant imatinib is superior in efficacy compared with 1 year of imatinib. Approximately 50% of deaths may be avoided during the first 10 years of follow-up after surgery with longer adjuvant imatinib treatment.

Trial registration: ClinicalTrials.gov Identifier: NCT00116935.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Joensuu has a coappointment at Orion Pharma, has received fees from Neutron Therapeutics, and owns stocks of Orion Pharma and Sartar Therapeutics. Dr Eriksson has acted as a consultant for Isofol Medical and participated in advisory boards for Bayer and Clinigen. Dr Hohenberger has participated to advisory boards for Roche and Pfizer. Dr Jost has a consulting or an advisory role, received honoraria, research funding, and/or travel/accommodation expenses from AbbVie, BMS, Boehringer, Novartis, Pfizer, Servier, and Celgene. Dr Al-Batran has an advisory role with Merck, Roche, Celgene, Lilly, Nordic Pharma, Bristol-Myers Squibb, Astellas, and Merck Sharp & Dohme; he is a speaker for Roche, Celgene, Lilly, Nordic Pharma, AIO gGmbH, MCI, ProMedicis, Forum für Medizinische Fortbildung, and Taiho Pharma; he is CEO/founder of IKF Klinische Krebsforschung GmbH at Northwest Hospital, and has received research grants from Sanofi, Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly, Eurozyto, German Cancer Aid (Krebshilfe), German Research Foundation, and the Federal Ministry of Education and Research. No other conflicts are reported.

Figures

Figure 1.. Kaplan-Meier Estimates of Survival Outcomes

A, Recurrence-free survival in the intention-to-treat population. B, recurrence-free survival in the efficacy population. C, Overall survival in the intention-to-treat population. D, Overall survival in the efficacy population.

Figure 2.. Recurrence-Free Survival in Prespecified Subgroups

GIST indicates gastrointestinal stromal tumor; (n) indicates the number of patients; (e) indicates the number of events (either GIST recurrence or death).