Abstract
Regorafenib is a multi-kinase cancer-cell proliferation receptor domain inhibitor (inhibition of KIT, PDGFR, RET), angiogenesis inhibitor (inhibition of VEGFR1-3, TIE2, EGF-like domain) and tumor microenvironment inhibitor (inhibition of FGFR, PDGFR). Currently, it is used as a standard third line therapy of advanced gastrointestinal stromal tumor.
According to the GRID registration study, progression free survival of 4.8 months was reached in the regorafenib group, compared with 0.9 months in the placebo group. Interestingly, the regorafenib efficacy was not dependent on the tumor mutation status (i.e, similar efficacy with adverse KIT gene exon 9 mutations and the wild-type allele).
Second standard indication fro regorafenib is advanced colorectal carcinoma after previous treatment with oxaliplatina, fluoropyrimidines, irinotekan, after anti-angiogenic treatment, and after anti-EGFR therapy in wild-type RAS cases. In these highly pre-treated patients, regorafenib significantly prolonged overall survival (OS) compared to the placebo group, both in the CORRECT registration study (6.4 months versus 5.0 months) and in the Asian CONCUR study (8.8 months versus 6.3 months).
There are also important data about the efficacy in patients with advanced hepatocellular carcinoma refractory to sorafenib treatment as well as data about changes in OS in patients with advanced colorectal carcinoma treated with second palliative line of treatment, depending on the treatment initiation sequence with regorafenib compared with cetuximab chemotherapy. The aim of ongoing studies is to evaluate regorafenib efficacy in the treatment of advanced billiary tract cancer, pancreatic cancer, and gastric and esophageal junction cancer.