A multi‐institutional phase 2 trial of regorafenib in refractory advanced biliary tract cancer

Background Regorafenib is an oral multikinase inhibitor targeting angiogenesis, oncogenesis, and cancer proliferation/metastasis. This study evaluated the efficacy of regorafenib in refractory biliary tract cancer (BTC) in a multi‐institutional phase 2 study. Methods Patients with BTC who progressed on at least 1 line of systemic therapy received regorafenib at 160 mg daily for 21 days on and 7 days off. The primary endpoint was 6‐month overall survival (OS), and the secondary endpoints were median OS, progression‐free survival (PFS), and objective response rates. Pretreatment plasma was collected for cytokine evaluation. Results A total of 39 patients were enrolled, and 33 were evaluable for efficacy. The median PFS and OS were 3.7 and 5.4 months, respectively, with survival rates of 46.2% at 6 months, 35.9% at 12 months, and 25.6% at 18 months for the intention‐to‐treat population. For the 33 evaluable patients who received regorafenib for at least 3 weeks, the median PFS and OS were 3.9 and 6.7 months, respectively, with survival rates of 51.5% at 6 months, 39.4% at 12 months, and 27.3% at 18 months. The objective response rate was 9.1%, and the disease control rate was 63.6%. Twenty‐eight patients (71.8%) experienced grade 3/4 adverse events. Among the 23 cytokines analyzed, elevated baseline vascular endothelial growth factor D (VEGF‐D) was associated with shorter PFS, whereas elevated baseline interleukin 6 (IL‐6) and glycoprotein 130 (GP130) were associated with shorter OS. Conclusions Regorafenib demonstrated modest clinical efficacy in heavily pretreated patients with BTC. Further exploration of biomarkers is warranted to identify a group of patients with BTC who may benefit from regorafenib. Regorafenib can provide modest clinical efficacy and a manageable safety profile in heavily pretreated patients with advanced biliary tract cancer.