Retrospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2024; 16(6): 2449-2462
Published online Jun 15, 2024. doi: 10.4251/wjgo.v16.i6.2449
Efficacy comparison of fruquintinib, regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer
Tian-Qi An, Hui Qiu, Quan-Bo Zhou, Hong Zong, Shuang Hu, Yu-Gui Lian, Rui-Hua Zhao
Tian-Qi An, Hong Zong, Shuang Hu, Rui-Hua Zhao, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
Hui Qiu, Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing 100000, China
Quan-Bo Zhou, Yu-Gui Lian, Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
Co-first authors: Tian-Qi An and Hui Qiu.
Co-corresponding authors: Yu-Gui Lian and Rui-Hua Zhao.
Author contributions: Zhao RH, Lian YG and Zong H conceptualized and designed the research; An TQ, Qiu H, Zhou QB and Hu S screened patients and acquired clinical data; Zhao RH, An TQ and Qiu H performed Data analysis; An TQ, Qiu H, Zhao RH, and Lian YG wrote the paper; All the authors have read and approved the final manuscript. An TQ and Qiu H were responsible for patient screening, enrollment, and collection of clinical data. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Both Zhao RH and Lian YG have played important and indispensable roles in the study design, data interpretation and manuscript preparation as the co-corresponding authors. Zhou QB searched the literature, revised and submitted the early version of the manuscript. Hu S and Zong H were instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search, preparation and submission of the current version of the manuscript. This collaboration between Hu S and Zong H is crucial for the publication of this manuscript and other manuscripts still in preparation.
Institutional review board statement: The study was approved by the Clinical Research Ethics Committee of the First Hospital of Zhengzhou University (No. 2022-KY-0910-001).
Informed consent statement: Patient informed consent was not needed as our study was retrospective.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data are publicly available for sharing use.
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: Rui-Hua Zhao, PhD, Chief Doctor, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450000, Henan Province, China. zrh_ly@163.com
Received: December 20, 2023
Revised: February 20, 2024
Accepted: April 7, 2024
Published online: June 15, 2024
Processing time: 178 Days and 0.5 Hours
Abstract
BACKGROUND

Regorafenib (R) and fruquintinib (F) are the standard third-line regimens for colorectal cancer (CRC) according to the National Comprehensive Cancer Network guidelines, but both have limited efficacy. Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair (MSS/pMMR) CRC. Due to the lack of studies comparing the efficacy between F, R, F plus programmed death-1 (PD-1) inhibitor, and R plus PD-1 inhibitors (RP), it is still unclear whether the combination therapy is more effective than monotherapy.

AIM

To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC (mCRC) patients in clinical practice.

METHODS

A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital, and 313 MSS/pMMR mCRC patients were finally included.

RESULTS

A total of 313 eligible patients were divided into F (n = 70), R (n = 67), F plus PD-1 inhibitor (FP) (n = 95) and RP (n = 81) groups. The key clinical characteristics were well balanced among the groups. The median progression-free survival (PFS) of the F, R, FP, and RP groups was 3.5 months, 3.6 months, 4.9 months, and 3.0 months, respectively. The median overall survival (OS) was 14.6 months, 15.7 months, 16.7 months, and 14.1 months. The FP regimen had an improved disease control rate (DCR) (P = 0.044) and 6-month PFS (P = 0.014) and exhibited a better trend in PFS (P = 0.057) compared with F, and it was also significantly better in PFS than RP (P = 0.030). RP did not confer a significant survival benefit; instead, the R group had a trend toward greater benefit with OS (P = 0.080) compared with RP. No significant differences were observed between the R and F groups in PFS or OS (P > 0.05).

CONCLUSION

FP is superior to F in achieving 6-month PFS and DCR, while RP is not better than R. FP has an improved PFS and 6-month PFS compared with RP, but F and R had similar clinical efficacy. Therefore, FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.

Keywords: Colorectal cancer, Fruquintinib, Regorafenib, Programmed death-1 inhibitor, Real-world

Core Tip: Fruquintinib (F) and regorafenib (R) monotherapy or in combination with programmed death-1 (PD-1) inhibitors, are commonly used treatment options for microsatellite stable or proficient mismatch repair (MSS/pMMR) colorectal cancer (CRC). Nowadays, there is limited research data comparing the efficacy of F plus PD-1 inhibitors (FP) and R plus PD-1 inhibitors (RP) to F and R monotherapy. And there is also no consensus on whether combination therapy is more effective than monotherapy. We included a total of 313 patients with MSS/pMMR metastatic CRC (mCRC) who received at least third-line treatment with F, R, FP, or RP at our hospital, and then conducted statistical analysis on their clinical data and prognosis. And then found that the FP regimen has the potential to yield favorable survival benefits for MSS/pMMR mCRC, making it worthy of further research and investigation.