Efficacy and Safety of Regorafenib in Korean Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib: A Multicenter Study Based on the Management Access Program

Abstract

PurposeThe aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients.Materials and MethodsFifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on/1 week off).ResultsNone of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a hand-foot skin reaction (n=31).ConclusionThis study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.

Phase II Trial of Continuous Regorafenib Dosing in Patients with Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib

“…Thus, although this trial was an uncontrolled study and had somewhat different patient characteristics from previous studies, DCR of 100 mg of regorafenib continuous administration was comparable to that of the standard dosing schedule (160 mg daily for 3 weeks followed by a 1‐week rest). The median PFS was 7.3 months (95% CI, 5.9–8.6) in the current study, whereas the median PFS in the GRID study and MAP trial was 4.8 months and 4.5 months, respectively . The median PFS in the current study was not shorter than that of prior studies using 160 mg daily intermittent dosing schedule (Table ).…”

“…In the current study, with regorafenib 100 mg daily continuous dosing, DCR lasting for at least 12 weeks was 64% (16 of 25 patients), which met the primary endpoint. DCR values in the GRID study and MAP trial were 52.6% and 44% for at least 12 weeks, respectively . Thus, although this trial was an uncontrolled study and had somewhat different patient characteristics from previous studies, DCR of 100 mg of regorafenib continuous administration was comparable to that of the standard dosing schedule (160 mg daily for 3 weeks followed by a 1‐week rest).…”

“…In this study, the exacerbation of symptoms occurred after stopping regorafenib and improved with the restart of regorafenib. All five patients who continued regorafenib during the rest period showed an improvement in their symptoms, and only one of them experienced a temporary exacerbation of drug‐related toxicity . A Japanese study also reported a patient with rectal GISTs, who experienced pain during a 1‐week resting period from regorafenib and improved with continuous administration of regorafenib .…”

“…However, tumors or tumor‐related symptoms may progress during the treatment off period. Son et al reported that 26% of patients experienced exacerbation of cancer‐related symptoms during the rest period. In this study, the exacerbation of symptoms occurred after stopping regorafenib and improved with the restart of regorafenib.…”

“…In addition, there are concerns that tumors and tumor‐related symptoms may progress during the off‐treatment period. In our previous study, approximately 26% of patients experienced an exacerbation of their cancer‐related symptoms during the rest period in the intermittent regorafenib regimen . Therefore, continuous administration of regorafenib at a lower dose could be a feasible and effective measure in preventing disease flare‐up during the off‐treatment period.…”