A multicenter cohort study of sunitinib (SU) versus imatinib (IM) dose escalation as second-line therapy in patients with gastrointestinal stromal tumors (GISTs) after disease progression of 400 mg/d IM.

Abstract

356 Background: Lacking of robust evidence from prospective trials, whether to choose IM dose escalation or to directly change to SU in patients failure on standardized 400mg/d dosing of IM is still controversial. Methods: The aim of this study, is to compare the efficacy of sunitinib and imatinib dose escalation as second-line therapy in patients with GIST previously treated with 400mg/d IM. Data of patients with recurrent/metastatic GISTs who was treated by SU from 2008.1 to 2016.12, in three tertiary teaching hospitals in southern China were analyzed from prospectively registered databases, respectively. Time to SU failure (TTSF) was defined as from the time of disease progression of 400mg/d IM to failure of SU treatment in both groups. Results: A total of 240 patients received SU at least 8 weeks were collected. SU was given in 37.5mg continuous daily dose or 50mg 4 weeks on/2 weeks off. Data of 203 patients (male 136, female 67) with complete follow-up were analyzed. The median age was 52.6 years, ranged 20-79 years. KIT/PDGFRA mutational analysis was performed in 151 patients. KIT exon 11 and 9 mutations were found in 79 (52.3%) and 39 (25.8%) patients, respectively. PDGFRA D842V was in five patients (3.3%), and KIT/PDGFRA WT in 26 patients (17.2%). After failure on 400mg/d IM, 100 (49.3%) patients had a dose escalation to 600mg/800mg per day (IM group), and 103 directly changed to SU(SU group). The progression-free survival (PFS) of IM group and SU group was 5.8m and 16.9m, respectively ( P<0.001). Either the TTSF or overall survival (OS) on both groups was not statistically different (18.3m VS 16.9m, P=0.219; 29.42m VS 29.45m, P=0.73). None of clinical factors that was correlated with survival using regress analysis, including primary site of lesion, metastatic sites, or mutational status, etc. Conclusions: This multi-center cohort study indicated better PFS in directly changed to SU than IM dose escalation when standardized dose IM failure. However, to those continued with SU therapy after failure of dose escalation, the outcome, both time to SU failure or OS, is similar.