Assessing a Regorafenib-irinotecan Combination Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients

A Phase III randomized trial that compared Nexiri (Nexavar® + Irinotecan) vs irinotecan or versus Sorafenib alone showed a progression‐free survival at two‐months which was favorable to the NEXIRI combination ; 59% ( IC95% : 39‐66 ) versus 23% (IC95% : 10‐33) and 22% (IC95%: 8‐30) respectively. The patients treated with Irinotecan or Sorafenib alone could receive NEXIRI combination after progression and the progression‐free survivals were 3,7 months (IC95% : 2,2‐4,9) and 3,5 months (IC95% : 2,1‐3,7) in patients treated with NEXIRI or after progression and 1,9 months (IC95% : 1,7‐2,1) and 2,1 months (IC95% : 1,9‐2,5) in patients treated only with Irinotecan and Sorafenib respectively. The median overall survival was higher with NEXIRI : 7,2 months (patients treated from the beginning of the study) and 7,9 months (patients treated after progression and crossover) versus 3 months in patients treated only with Irinotecan and 3,2 months in patients receiving only Sorafenib. The A870A rs603965 polymorphism of cyclin D1, a molecule involved in the initiation of cell division, was favorable to the NEXIRI combination on overall survival with a median of 19.6 months versus 6.2 months for two other genotypes A/G and G/G. Regorafenib, which is an oral signal deactivation agent with a chemical structure very similar to Sorafenib, is a standard treatment in heavily pretreated mCRC patients since the results of CORRECT study which compared Regorafenib to placebo on overall survival showed a superiority of Regorafenib : 6,4 months versus 5 months (HR 0,774 [IC95% 0,63, 0,94]). Sorafenib isn't approved in mCRC so the objective of this NEXT‐REGIRI trial is compared REGIRI combination (Regorafenib‐Irinotecan) to Regorafenib alone in a phase III trial in patients in progression after having received all standard treatments and bearing genotype A/A of cyclin D1