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

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Kim, RD; Sanoff, HK; Poklepovic, AS; Soares, H; Kim, J; Lyu, J; Liu, Y; Nixon, AB; Kim, DW

Published Date

  • August 1, 2020

Published In

Volume / Issue

  • 126 / 15

Start / End Page

  • 3464 - 3470

PubMed ID

  • 32453456

Pubmed Central ID

  • PMC7787270

Electronic International Standard Serial Number (EISSN)

  • 1097-0142

Digital Object Identifier (DOI)

  • 10.1002/cncr.32964


  • eng

Conference Location

  • United States