Systematic Review of Escalated Imatinib Doses Compared with Sunitinib or Best Supportive Care, for the Treatment of People with Unresectable/Metastatic Gastrointestinal Stromal Tumours Whose Disease has Progressed on the Standard Imatinib Dose

Abstract

IntroductionWe conducted a systematic review of evidence on the effectiveness of imatinib at escalated doses of 600 mg/day or 800 mg/day for treatment of adults with unresectable or metastatic gastrointestinal stromal tumours (GIST), following progression on imatinib at the 400 mg/day dose, compared with sunitinib and/or ‘best supportive care’.MethodsElectronic searches were undertaken to identify relevant randomised controlled trials (RCTs), non-randomised studies, and case series reporting outcome data on survival, quality of life or adverse events. Titles and abstracts were screened by two reviewers and full text reports of potentially relevant studies assessed for inclusion. Included studies were quality assessed by two reviewers and data were extracted. Five studies reported data on the relevant population and were included.Results and DiscussionMedian overall survival for imatinib (800 mg/day) and sunitinib both were less than 2 years. Around 25% of patients required either an imatinib dose delay or reduction. Approximately one-third of patients receiving dose escalated imatinib (either dose) showed either response or stable disease. Amongst those responding to the escalated 800 mg/day dose, median progression-free survival was over 25 months. The statistical likelihood of response may depend on exon mutational status. There were few data and those that were available were potentially biased, due to their non-randomised nature. Further data are needed to justify international guideline recommendations on imatinib dose escalation.ConclusionA prospective audit of management and outcomes for unresectable GIST patients treated with dose escalation upon progression at 400 mg/day may be appropriate as an RCT may be unfeasible.

Current management of gastrointestinal stromal tumors: Surgery, current biomarkers, mutations, and therapy

“…A systematic review of randomized and nonrandomized studies to evaluate the efficacy of imatinib after dose escalation (600 mg/day or 800 mg/day) concluded that 1 in 3 patients had either a partial response or stable disease after the escalation of imatinib dose, and that 58.7% of these patients remained progression-free at 2 years' follow-up. 67 Another option for patients who are intolerant or resistant to imatinib is the multitargeted TKI sunitinib. Sunitinib inhibits c-KIT and PDGFR and other kinases, including the vascular endothelial growth factor receptors.…”

State of the Art in the Treatment of Gastrointestinal Stromal Tumors

“…Escalating the imatinib dose to 800 mg per day in this progressing population was demonstrated to achieve response or disease stabilization in one third of patients in a recent systematic review of published data [79], and this approach is considered as the treatment standard by many oncologists, although all of the available evidence is based on retrospective, observational studies. Sunitinib, a multi-TKI active against KIT, platelet-derived growth factor receptors and vascular endothelial growth factor receptors, is the standard treatment for patients progressing on or intolerant to imatinib.…”

Systemic therapy options for advanced gastrointestinal stromal tumors beyond first-line imatinib: a systematic review

“…Median OS for imatinib (800 mg/day) and sunitinib both were less than 2 years. However, there were few data in this systematic review and those that were available were potentially biased, due to their nonrandomized nature [42].…”