Sunitinib therapy for imatinib-resistant and/or intolerant gastrointestinal stromal tumors: comparison of safety and efficacy between standard and reduced dosage regimens.

Abstract

Sunitinib therapy for patients with imatinib-resistant and/or intolerant gastrointestinal stromal tumors (GISTs) often causes severe adverse events (AEs) that lead to treatment discontinuation. We retrospectively reviewed the clinical records of imatinib-resistant and/or intolerant GIST patients who underwent sunitinib therapy in our institutions between 2007 and 2020. Forty-one patients were enrolled and divided into two groups on the basis of the starting dosage: the standard dosage group (50mg/day, 21 patients) and the reduced dosage group (37.5mg/day, 20 patients). Tolerability, safety and clinical efficacy of the two groups were compared. Three patients (14%) in the standard dosage group and another three (15%) in the reduced dosage group (P=1.000) discontinued sunitinib therapy because of AEs. The incidences of grade 3 or more severe treatment-related AEs were 90 and 75%, respectively (P=0.238). Two possible treatment-related deaths were noted in the standard dosage group. Clinical efficacy was comparable between the two groups: median time to treatment failure and overall survival were 4.5months [interquartile range (IQR), 3.6-9.0] and 13.7months (IQR, 7.5-22.9) in the standard dosage group and 4.6months (IQR, 2.7-17.0) and 13.4months (IQR, 9.3-36.8) in the reduced dosage group, respectively. The reduced dosage of 37.5mg sunitinib tended to decrease toxicity and the incidences of severe AEs and treatment-related deaths. This reduced dosage regimen showed equivalent clinical efficacy including patient survival. The reduced dosage of 37.5mg sunitinib can be adopted as an alternative therapy for patients with imatinib-resistant and/or intolerant GISTs.