Real-World Results of Raltitrexed Combined with S-1 and Bevacizumab in Heavily Pretreated Metastatic Colorectal Cancer

Abstract

Purpose

Treatment options for refractory metastatic colorectal cancer (CRC) are scarce. This retrospective study aimed to evaluate the efficacy and safety of raltitrexed combined with S-1 and bevacizumab in patients with heavily pretreated metastatic CRC in a clinical real-world setting.

Patients and Methods

Records of patients with metastatic CRC refractory to standard therapies who initiated raltitrexed plus S-1 and bevacizumab from October 2017 to December 2021 were retrospectively reviewed at our institution. The study endpoints included median overall survival (OS), overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs).

Results

Forty-four patients with metastatic CRC, who had previously undergone standard chemotherapy received the regimen comprising raltitrexed plus S-1 and bevacizumab. As of March 2022, the median follow-up was 23.2 months (95% confidence interval 15.8−30.6). The median OS and median PFS were 13.5 (95% CI 9.9–17.1) and 4.7 months (95% CI 3.6–5.8), respectively, with a 16-week PFS rate of 60.9%. Among 43 patients with measurable lesions, the ORR and DCR were 7.0% (3/43) and 65.1% (28/43), respectively. Patients without peritoneal metastases (P = 0.003, hazard ratio 0.160, 95% CI 0.048−0.531), lower carcinoembryonic antigen level (≤42.8 ng/mL) (P = 0.039, HR 0.382, 95% CI 0.153−0.952), and no previous treatment with both vascular endothelial growth factor inhibitors (VEGF) and S-1 (P = 0.020, HR 0.215, 95% CI 0.059−0.785) had better OS. The incidence of any grade of treatment-related AEs was 88.6%, most of which were mild to moderate, and no treatment-related deaths occurred.

Conclusion

Raltitrexed combined with S-1 and bevacizumab shows promising antitumor activity and safety and could be an alternative for patients with metastatic CRC who are refractory or intolerant to standard therapy.

Keywords:

• refractory metastatic colorectal cancer
• chemotherapy
• target therapy
• angiogenesis

Abbreviations

CRC, Colorectal cancer; OS, Overall survival; ORR, Objective response rate; PFS, Progression-free survival; DCR, Diseases control rate; AEs, Adverse events; CI, confidence interval; VEGF, vascular endothelial growth factor inhibitors; MSI, microsatellite instability; MMR, mismatch repair; TKI, tyrosine kinases inhibitor; ECOG, Eastern Cooperative Oncology Group; CR, complete response; PR, partial response; CEA, carcinoembryonic antigen; LMR, lymphocyte/monocyte ratio; HR, hazard ratios; EGFR, epidermal growth factor receptor; TRAEs, Treatment-related AEs; BID, bis in die.

Data Sharing Statement

All data and/or materials used during this study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

All procedures performed in this study were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments. This study was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences, and Peking Union Medical College (approval number: 2022062208472502). Given that this was a retrospective study, the requirement for informed consent was waived by the Ethics Committees of the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences, and Peking Union Medical College. Patient data was anonymized for confidentiality.

Acknowledgments

We would like to express our sincere thanks to all the team members who provided help during the research process. Thanks also to the Editage (www.editage.cn) for English language editing. No financial support was received for the study, authorship, and/or publication of this paper.

Author Contributions

All authors made a significant contribution to conception, study design, execution, acquisition of data, analysis, and interpretation or in all these areas; took part in drafting, revising or critically reviewing the article; have agreed on the journal to which the article was submitted, gave the final version accepted for publication and agree to take responsibility for the contents of the work.

Disclosure

All authors have no conflict of interest regarding this study.

Additional information

Funding

This work was supported by the Development Project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MODP2022002).