Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2022; 14(4): 920-934
Published online Apr 15, 2022. doi: 10.4251/wjgo.v14.i4.920
Regorafenib combined with programmed cell death-1 inhibitor against refractory colorectal cancer and the platelet-to-lymphocyte ratio’s prediction on effectiveness
Yu-Jie Xu, Peng Zhang, Jin-Long Hu, Hong Liang, Yan-Yan Zhu, Yao Cui, Po Niu, Min Xu, Ming-Yue Liu
Yu-Jie Xu, Jin-Long Hu, Yan-Yan Zhu, Yao Cui, Po Niu, Ming-Yue Liu, Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
Peng Zhang, Hong Liang, Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
Min Xu, Department of Hepatology, The Third People's Hospital of Zhengzhou, Zhengzhou 450003, Henan Province, China
Author contributions: Liu MY and Xu YJ designed the research; Xu YJ, Zhang P, and Hu JL performed the research; Liang H, Zhu YY, and Cui Y contributed new reagents/analytic tools; Xu YJ, Zhang P, Niu P, and Xu M analyzed the data; Liu MY, Xu YJ, and Zhang P wrote the paper.
Supported by the Henan Provincial Department of Science and Technology, No. 212102310047.
Institutional review board statement: This study was approved by the ethics committee of People’s Hospital of Zhengzhou University (Henan Province, China) and performed in accordance with the Declaration of Helsinki.
Informed consent statement: The requirement for informed consent was waived by the committee because of the retrospective nature of the study.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Yue Liu, Doctor, MD, PhD, Chief Doctor, Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, Henan Province, China. 1816160187@e.gzhu.edu.cn
Received: October 9, 2021
Peer-review started: October 9, 2021
First decision: December 12, 2021
Revised: January 4, 2022
Accepted: March 25, 2022
Article in press: March 25, 2022
Published online: April 15, 2022
Abstract
BACKGROUND

The effectiveness of regorafenib plus programmed cell death-1 (PD-1) inhibitor in treating microsatellite stable (MSS) metastatic colorectal cancer (mCRC) remains controversial.

AIM

To investigate the benefits of regorafenib combined with PD-1 inhibitor in treating MSS mCRC and explore indicators predicting response.

METHODS

This retrospective study included a total of 30 patients with microsatellite stable metastatic colorectal cancer treated with regorafenib combined with programmed cell death-1 inhibitor at Henan Provincial People’s Hospital between December 2018 and December 2020. During a 4-wk treatment cycle, regorafenib was performed for 3 continuous weeks. PD-1 inhibitor was intravenously injected starting on the first day of the oral intake of regorafenib. We reviewed tumor response, progression-free survival (PFS), overall survival, and treatment-related adverse events (TRAEs) and evaluated association between platelet-to-lymphocyte ratio (PLR) and outcomes in this retrospective study.

RESULTS

Stable disease and progressive disease were found in 18 (60.0%) and 12 (40.0%) patients, respectively. The disease control rate was 60.0%. The median follow-up time was 12.0 mo, and median PFS was 3.4 mo [95% confidence interval (CI): 2.2-4.6 mo]. Of the 12 patients with progressive disease, 10 (83.3%) had liver metastasis before starting the combined treatment. Among the 18 patients with SD, 10 (55.6%) did not have liver metastases. One patient without liver metastases at baseline was found with a substantially prolonged PFS of 11.2 mo. The liver metastasis, the choice of programmed cell death-1 inhibitor other than nivolumab or pembrolizumab and previous exposure to regorafenib was’t associated with treatment outcome. The median PFS in the low-PLR group was 4.2 mo (95%CI: 3.5-4.9 mo), compared with 2.8 mo (95%CI: 1.4-4.2 mo) in the high-PLR group (P = 0.005). The major TRAEs included hand-foot syndrome (33.3%), hypertension (23.3%), malaise (20.0%), and gastrointestinal reaction (16.7%). The incidence of grade 3 TRAEs was 13.3% (4/30), which comprised abnormal capillary proliferation (n = 1), transaminase elevation (n = 1), and hand-foot syndrome (n = 2). No grade 4 or higher toxicity was observed.

CONCLUSION

Regorafenib combined with PD-1 inhibitor could lead to a longer PFS in some patients with MSS mCRC. The PLR might be a prediction of the patient response to this therapy.

Keywords: Colorectal neoplasms, Microsatellite stable, Programmed cell death-1 inhibitor, Platelet-to-lymphocyte ratio, Regorafenib, Progression-free survival

Core Tip: The use of regorafenib combined with programmed cell death-1 inhibitor in the treatment of refractory microsatellite stable colorectal cancer has contradictory results in some small-scale studies. The purpose of this paper is to analyze the real-world data of our center in the past 2 years so as to provide more treatment experience and reference for treatment selection. The progression-free survival and overall survival of patients with refractory microsatellite stable colorectal cancer treated with regorafenib combined with programmed cell death-1 inhibitor were analyzed retrospectively, and the safety and adverse reactions under different doses were reviewed. The platelet-to-lymphocyte ratio was found as a potential screening index for patients with prolonged progression-free survival.