Abstract
BACKGROUND: Regorafenib at the standard intermittent dosing schedule proved effective in the GRID trial for refractory gastrointestinal stromal tumors (GISTs). However, this dosing schedule requires frequent dose reduction, and the progression of GISTs or tumor-related symptoms during the off-treatment period has also been noted in some patients. Therefore, we conducted this phase II trial to evaluate the efficacy and safety of regorafenib at a lower dose on a continuous dosing schedule. METHODS: Patients with measurable, metastatic, or recurrent GISTs who failed to respond to both imatinib and sunitinib were eligible for this study. Regorafenib 100 mg p.o. daily was administered continuously. The primary endpoint was disease control rate (DCR: complete response plus partial response [PR] plus stable disease [SD]) lasting for at least 12 weeks using RECIST version 1.1. RESULTS: The best response was PR in 2 (8%), SD in 16 (64%), and progressive disease in 6 (24%) patients. DCR lasting for at least 12 weeks was 64% (16 of 25). The median progression-free survival was 7.3 months (95% confidence interval, 5.9-8.6), and the 1-year survival rate was 64.5%. Ten patients (40%) experienced grade 3-4 toxicities, including hand-foot skin reaction (n = 4, 16%) and elevation of alanine aminotransferase (n = 2, 8%). Only six patients (24%) needed dose modification with a relative dose intensity of 95.0% for eight cycles in all patients. CONCLUSION: Regorafenib at a lower dose on a continuous schedule might be an alternative treatment in patients with GISTs after failure of imatinib and sunitinib. Clinical trial identification number. NCT02889328 IMPLICATIONS FOR PRACTICE: Regorafenib at the standard intermittent dosing schedule proved effective in the GRID trial for refractory gastrointestinal stromal tumors (GISTs). However, this dosing schedule requires frequent dose reduction, and the progression of GISTs or tumor-related symptoms during the off-treatment period has been noted in some patients. This study was to evaluate the efficacy and safety of regorafenib at a lower dose on a continuous dosing schedule. With good efficacy and acceptable safety profiles, regorafenib at a lower, continuously administered dose might be an alternative treatment in patients with GISTs after imatinib and sunitinib. Rechallenge of regorafenib may slow the disease progression.