Abstract: Objective To evaluate the efficacy and safety of Regorafenib combined with PD?1 inhibitors for the third?line or above treatment of advanced microsatellite stable (MSS) colorectal cancer (CRC). Methods A total of 22 patients with advanced MSS CRC, who received Regorafenib combined with PD?1 inhibitors or Regorafenib monotherapy for third?line or above treatment in Renmin Hospital of Wuhan University from January 2019 to March 2022, were selected as the research objects, including 10 patients in the combination therapy group and 12 patients in the Regorafenib monotherapy group. The progression?free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and incidence of adverse events (AEs) were compared between the two groups. Results Kaplan?Meier survival analysis showed that there was no significant difference in median OS between the combination therapy group and the monotherapy group (6.10 months vs 6.13 months, P=0.827). However, the combination therapy group had better median PFS than the monotherapy group (4.00 months vs 1.63 months, P=0.025), and the DCR in combination therapy group were also better than the monotherapy group, though there was no statistical significance (70.0% vs 25.0%, P=0.084). No grade 4 or higher AEs were observed in either group. The overall incidence of AEs (100.0% vs 91.7%) and the incidence of grade ≥3 AEs (30.0% vs 25.0%) were not statistically different between the combination therapy group and the monotherapy group (all P>0.05). Conclusions  Compared with Regorafenib monotherapy, Regorafenib combined with PD?1 inhibitors as the third?line or above treatment regimen for advanced MSS CRC may bring benefits for PFS, and it is worthy of further clinical trials.

Key words: Colorectal cancer, Regorafenib, PD-1 inhibitors, Microsatellite stable, Efficacy, Safety