Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study

Caiyun Nie; Huifang Lv; Beibei Chen; Weifeng Xu; Jianzheng Wang; Yingjun Liu; Saiqi Wang; Jing Zhao; Yunduan He; Xiaobing Chen

doi:10.3389/fonc.2022.917353

Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study

Front Oncol. 2022 Sep 26:12:917353. doi: 10.3389/fonc.2022.917353. eCollection 2022.

Authors

Caiyun Nie^{1

2

3

4}, Huifang Lv^{1

2

3

4}, Beibei Chen^{1

2

3

4}, Weifeng Xu^{1

2

3

4}, Jianzheng Wang^{1

2

3

4}, Yingjun Liu⁵, Saiqi Wang^{1

2

3

4}, Jing Zhao^{1

2

3

4}, Yunduan He^{1

2

3

4}, Xiaobing Chen^{1

2

3

4}

Affiliations

¹ Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
² State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.
³ Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer, Zhengzhou, China.
⁴ Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer, Zhengzhou, China.
⁵ Department of General Surgery, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Objectives: The antitumor activity of nivolumab plus regorafenib in colorectal cancer from a phase Ib REGONIVO study is encouraging. The present study was conducted to evaluate the efficacy and safety of regorafenib or fruquintinib plus sintilimab as third-line or above therapy in patients with microsatellite stable (MSS) metastatic colorectal cancer.

Methods: Patients with MSS metastatic colorectal cancer who have failed from prior treatment and received regorafenib or fruquintinib plus sintilimab as third-line or above therapy from January 2019 to December 2020 were prospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

Results: 42 patients received regorafenib plus sintilimab(RS), and the other 30 patients received fruquintinib plus sintilimab(FS). In the general population, the ORR and DCR were 13.9% and 70.8%, and the median PFS and OS was 4.2(95% CI=2.9-5.5) and 10.5 (95% CI=8.6-12.4) months, respectively. There were no statistically significant differences between RS and FS group in PFS (3.5(2.2-4.8) vs. 5.5(3.5-7.5) months, P=0.434) and OS (11.0(7.0-15.0) vs. 10.5(3.8-17.2) months, P=0.486). Subgroup analysis suggested that patients without liver metastasis responded well to this combination regimen (ORR: 21.4% vs. 9.1%) and obtained better OS (26(8.8-43.2) vs. 10.0(7.4-12.6) months, P=0.016). The incidence of Grade 3-4 adverse events (AEs) was 15.3% and the toxicities were generally tolerable and manageable.

Conclusions: Regorafenib or fruquintinib plus sintilimab as third-line or above therapy provide a feasible treatment regimen for MSS metastatic colorectal cancer with tolerated toxicity. Patients without liver metastasis may be the preferred population for this combination regimen.

Keywords: colorectal cancer; immunotherapy; liver metastasis; microsatellite stable; targeted therapy.