The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study

Jisheng Li, Lei Cong, Jintao Liu, Ling Peng, Jun Wang, Alei Feng, Jinbo Yue, Li Li, Xiuwen Wang, Xiangling Wang, Jisheng Li, Lei Cong, Jintao Liu, Ling Peng, Jun Wang, Alei Feng, Jinbo Yue, Li Li, Xiuwen Wang, Xiangling Wang

Abstract

Background: Microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. However, a recent Japanese trial showed that regorafenib plus nivolumab had encouraging anti-cancer activity in MSS or pMMR mCRCs.

Materials and methods: We retrospectively reviewed the efficacy and safety data of combination therapy with regorafenib plus anti-PD-1 antibody in patients with refractory MSS or pMMR mCRC in the medical centers of Shandong Province in China.

Results: Twenty-three patients with MSS or pMMR mCRC received regorafenib plus anti-PD-1 antibody. Eighteen (78.3%) patients experienced stable disease as best response, five (21.7%) patients had progressive disease, and no partial response was observed. The disease control rate (DCR) was 78.3% (18/23), and the median progression-free survival (PFS) was 3.1 months (95% CI, 2.32-3.89). Four of five (80.0%) patients with progressive disease had baseline liver metastasis, while nine of 18 (50.0%) patients with stable disease displayed no liver metastasis. One patient receiving radiofrequency ablation treatment for liver and abdominal wall metastases prior to combination treatment experienced a remarkably prolonged PFS of 9.2 months with SD. Neither liver metastasis status nor previous exposure to regorafenib was associated with treatment outcome. Treatment-related grade 3 toxicities were observed in 5/23 (21.7%) patients.

Conclusion: No objective response was observed with the combination of regorafenib plus anti-PD-1 antibody, suggesting its little clinical activity in unselected Chinese patients with pMMR/MSS mCRC. Meanwhile, it exhibited some potential benefit in this cohort in terms of DCR and PFS. Adverse events were generally tolerable and manageable. Prospective studies with large sample sizes are needed to verify the findings. This combination strategy plus local ablative therapy might be worthy of further exploration.

Keywords: PD-1; colorectal cancer; immune checkpoint inhibitor; microsatellite stable; regorafenib.

Copyright © 2020 Li, Cong, Liu, Peng, Wang, Feng, Yue, Li, Wang and Wang.

Figures

Figure 1
Figure 1
Kaplan–Meier survival curves. (A) PFS of 21 evaluable patients. (B) OS of the whole cohort. (C) PFS in patients with or without liver metastasis (p > 0.05). (D) PFS in patients with or without previous exposure to regorafenib (rego) (p > 0.05). Data cut-off date for survival results was July 15, 2020.

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Source: PubMed

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