Real-world outcomes of regorafenib combined with immune checkpoint inhibitors in patients with advanced or metastatic microsatellite stable colorectal cancer: A multicenter study

Kaili Yang, Lu Han, Shikai Wu, Xiujuan Qu, Qin Li, Chuanhua Zhao, Jing Zhou, Xuan Jin, Yusheng Wang, Dong Yan, Zhiqiang Cheng, Yuwei Hua, Yan Zhang, Yang Ge, Jinghua Sun, Wei Deng, Lin Zhao, Yunbo Zhao, Kaili Yang, Lu Han, Shikai Wu, Xiujuan Qu, Qin Li, Chuanhua Zhao, Jing Zhou, Xuan Jin, Yusheng Wang, Dong Yan, Zhiqiang Cheng, Yuwei Hua, Yan Zhang, Yang Ge, Jinghua Sun, Wei Deng, Lin Zhao, Yunbo Zhao

Abstract

Background: Treatment strategies are limited for patients with chemotherapy refractory microsatellite stable (MSS) colorectal cancer. We aim to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with regorafenib in this population in routine clinical practice.

Methods: We retrospectively analyzed patients with advanced or metastatic colorectal cancer who received at least one dose of ICIs combined with regorafenib in 14 Chinese medical centers. The primary outcome was objective response rate (ORR). This study was registered at ClinicalTrials.gov on February 2020 (NCT04771715).

Results: Eighty-four patients received ICIs combined with regorafenib from January 2019 to January 2021. Most patients (91%) received two or more systemic treatment lines before the study treatment. Seventy-six patients (90%) had confirmed MSS status. At a median follow-up of 5.5 months, four patients achieved partial response (5%) and 37 patients achieved stable disease (45%) as the best response. The median progression-free survival (PFS) was 3.1 months, and the median overall survival was 17.3 months. Eleven patients (13%) remained progression-free for more than 6 months. Baseline liver metastasis (HR 1.98, 95%CI 1.07-3.69, P = 0.03) and neutrophil-lymphocyte ratio (NLR) of ≥ 1.5 (HR 2.83, 95%CI 1.00-7.98, P = 0.05) were associated with shorter PFS in multivariate analysis. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 16 patients (19%).

Conclusion: The combination of ICIs with regorafenib can be a valuable treatment option for a proportion of patients with chemotherapy refractory MSS colorectal cancer. Patients with no liver metastasis and a low NLR at baseline may derive most benefit from this strategy.

Keywords: Colorectal cancer; Combination therapy; Immune checkpoint inhibitor; Real world; Regorafenib.

Conflict of interest statement

The authors declared no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Forest plot of univariate analysis for (A) disease control rate and (B) progression-free survival CI Confidence interval; ECOG PS Eastern Cooperative Oncology Group Performance Status; EGFR epidermal growth factor receptor; HR hazard ratio; ICI immune checkpoint inhibitor; NLR neutrophil–lymphocyte ratio; OR odds ratio; VEGF vascular endothelial growth factor
Fig. 2
Fig. 2
Kaplan–Meier curves of (A) progression-free survival (n = 83) and (B) overall survival (n = 84) in patients with colorectal cancer treated with immune checkpoint inhibitors plus regorafenib

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