Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2025; 31(29): 109947
Published online Aug 7, 2025. doi: 10.3748/wjg.v31.i29.109947
Targeted therapy combined with immunotherapy vs trifluridine/tipiracil with bevacizumab as late-line therapy in metastatic colorectal cancer
Zhao Gao, Xiao-Yan Wang, Tao Song, Zhi-Gang Shen, Xiao-Yun Wang, Shi-Kai Wu, Xuan Jin
Zhao Gao, Xiao-Yun Wang, Shi-Kai Wu, Xuan Jin, Department of Medical Oncology, Peking University First Hospital, Beijing 100034, China
Xiao-Yan Wang, Tao Song, Zhi-Gang Shen, Department of Pharmacy, Jilin Cancer Hospital, Changchun 130012, Jilin Province, China
Author contributions: Gao Z wrote the manuscript; Jin X and Wu SK conceived of the review and edited the manuscript; Gao Z and Wang XY collected and analyzed the data; Shen ZG, Song T, Wang XY and Wu SK analyzed the data; Gao Z, Wang XY, Song T, Shen ZG, Wang XY, Wu SK, Jin X read and approved the final manuscript.
Supported by the National High Level Hospital Clinical Research Funding (Multi-Center Clinical Research Project of Peking University First Hospital), No. 2022CR65.
Institutional review board statement: This study has been approved by the Ethics Committee of Peking University First Hospital (approval No. 2025R0190-0001) and Jilin Cancer Hospital (approval No. 202501-003-01).
Informed consent statement: Consent to participate not required.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: Xuan Jin, PhD, Department of Medical Oncology, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China. jinxuanbdyy@outlook.com
Received: May 26, 2025
Revised: June 9, 2025
Accepted: July 11, 2025
Published online: August 7, 2025
Processing time: 71 Days and 1 Hours
Abstract
BACKGROUND

Targeted therapy combined with anti-programmed cell death 1 immunotherapy (TP) and trifluridine/tipiracil (TAS-102) combined with bevacizumab (TB) are two common therapies for patients with late-line therapy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). However, it is still unclear which therapy can bring better prognosis.

AIM

To evaluate the effectiveness and safety of TP vs TB as the late-line regimen for MSS mCRC in the real world.

METHODS

This is a dual-center retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital. Patients with MSS mCRC who had received at least the second line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two cohorts. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate PFS and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Landmark analysis was performed to create segmented survival curves, studying the impact of treatment regimen on prognosis during different follow-up periods.

RESULTS

Between July 2019 and March 2025 (data cutoff), 127 eligible patients were enrolled, with 88 and 39 patients assigned to the TP and TB cohorts, respectively, based on treatment allocation. At a global median follow-up of 9.73 months, the crude median PFS was 3.9 months (95%CI: 3.03-5.53) in the TP cohort vs 4.17 months (95%CI: 2.87-5.6) in the TB cohort, yielding a nonsignificant HR of 1.43 (95%CI: 0.94-2.18, P = 0.092; TB as reference). Multivariate Cox regression analysis, adjusted for sex, age > 60 years, Eastern Cooperative Oncology Group performance status, RAS mutation, primary tumor location (left vs right), number of metastatic organs (liver/lung), and treatment line (≥ 3rd line), demonstrated an adjusted HR of 1.23 (95%CI: 0.80-1.88, P = 0.348). PS-based analyses using three methodologies: Inverse probability weighting, PS matching (post-matching n = 55 vs 30), and PS-adjusted multivariate Cox regression. These analyses revealed consistent nonsignificant trends favoring TB, with HRs for TP of 1.26 (95%CI: 0.76-2.10, P = 0.077), 1.42 (95%CI: 0.87-2.34, P = 0.164), and 1.26 (95%CI: 0.76-2.10, P = 0.367), respectively. Notably, landmark PFS analyses at 90, 120, and 150 days demonstrated a significantly higher proportion of TP patients maintaining disease control beyond these timepoints (P = 0.048, 0.031, and 0.035, respectively), suggesting sustained clinical benefits in TP responders.

CONCLUSION

TP and TB demonstrated similar PFS in both crude and PS-adjusted analyses. However, patients who derived benefits from TP therapy exceeding 90 days showed more sustained clinical advantages compared to TB. Our study suggests that for patients with MSS mCRC who respond to TP therapy in later-line treatments, this regimen could provide additional prolonged clinical benefits, which warrants further validation through large-scale cohort investigations.

Keywords: Microsatellite stable; Metastatic colorectal cancer; Immune checkpoint inhibitors; Targeted therapy; Programmed cell death 1; Trifluridine/tipiracil

Core Tip: Targeted therapy combined with anti-programmed cell death 1 immunotherapy (TP) and trifluridine/tipiracil combined with bevacizumab (TB) are two common therapies for patients with late-line therapy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). However, it is still unclear which therapy can bring better prognosis. This study aims to evaluate the effectiveness and safety of TP vs TB as the late-line regimen for MSS mCRC in the real world.