Sunitinib malate for gastrointestinal stromal tumour in imatinib mesylate–resistant patients: recommendations and evidence

[摘要] Question Is sunitinib malate-marketed as Sutent (Pfizer Canada, Kirkland, QC)-superior to placebo or other interventions for primary outcomes of interest in adult patients with gastrointestinal stromal tumour (GIST) who have developed resistance or who exhibit intolerance to imatinib mesylate (IM)? BackgroundIn patients with resectable disease, surgery is the mainstay of treatment for GIST; in patients with unresectable or metastatic disease, the tyrosine kinase inhibitor IM is the therapy of choice. However, some patients have primary resistance or intolerance to IM, or they progress after optimal exposure (including an escalated dose). Here, we review the evidence for treating IM-resistant GIST with sunitinib malate. MethodsStudies of sunitinib malate were identified through MEDLINE, EMBASE, the Cochrane Library databases, and Web sites of guideline organizations. Outcomes of interest included time to progression, progression-free survival, overall survival, and toxicity. ResultsOne phase iii randomized controlled trial, and one abstract and presentation describing that trial, served as the evidentiary base for this clinical practice guideline. Trial data confidently show that both time to progression and progression-free survival are highly statistically significant ( p p= 0.007; absolute difference in weeks not reported). The most frequent of all adverse effects (experienced in greater proportion by patients on sunitinib malate) were grades 1 and 2 leucopenia (52% vs. 5% with placebo), neutropenia (43% vs. 4%), and thrombocytopenia (36% vs. 4%). Grade 3 hematologic adverse events were also reported more frequently in the sunitinib malate group, including leucopenia (4% vs. 0%), neutropenia (8% vs. 4%), lymphopenia (9% vs. 2%), and thrombocytopenia (4% vs. 0%). Toxicity comparisons did not includepvalues.The incidence of grades 1-3 fatigue was greater for the sunitinib malate group (34% vs. 22% with placebo). Other grade 3 nonhematologic treatment-related adverse events that occurred more frequently on sunitinib malate included hand-foot syndrome (4% vs. 0%), diarrhea (3% vs. 0%), and hypertension (3% vs. 0%). No grade 4 adverse events were observed. ConclusionsIn the target population, sunitinib malate is the recommended option for second-line therapy of metastatic GIST.  

[学科分类] 肿瘤学