Regorafenib with or without a programmed cell death protein 1 antibody as third-line treatment for microsatellite stable metastatic colorectal cancer

Purpose: Although the use of regorafenib plus nivolumab demonstrates promising outcomes in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC), other studies failed to observe such an effect. In addition, a comparison between regorafenib combined with programmed cell death protein 1 (PD-1) antibodies and regorafenib monotherapy has rarely been reported. The aim of this study was to assess whether regorafenib combined with a PD-1 antibody is superior to regorafenib monotherapy as third-line treatment for MSS mCRC. Methods Patients with MSS mCRC who received regorafenib combined with a PD-1 antibody or regorafenib monotherapy as third-line treatment were eligible for inclusion. Results In total, 179 patients were enrolled, of which 95 administered regorafenib combined with a PD-1 antibody and 84 administered regorafenib monotherapy. Overall, patients who administered regorafenib combined with a PD-1 antibody had similar progression-free survival (PFS) outcomes as those on regorafenib monotherapy (median PFS was 2.4 months and 1.9 months, respectively, P  = 0.086). The administration of regorafenib combined with a PD-1 antibody showed significantly longer PFS than regorafenib monotherapy in both male (5.2 months vs . 2.4 months, P  = 0.001) and female (3.9 months vs . 1.8 months, P  = 0.037) patients without liver metastasis. Unexpectedly, female patients with liver metastasis who administered regorafenib combined with a PD-1 antibody showed inferior PFS outcomes than those who administered regorafenib monotherapy (1.8 months vs. 2.0 months, P  = 0.030). Conclusion Liver metastasis and gender were predictors of survival benefit following the addition of a PD-1 antibody to regorafenib in patients with MSS mCRC.