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Second-line systemic treatment for metastatic colorectal cancer: A systematic review and Bayesian network
Chengyu Sun1, Enguo Fan2, Luqiao Huang1
1Department of Colorectal Surgery, The Affiliated Xuzhou Clinical College of Xuzhou Medical University, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
Plos One
|December 23, 2024
Summary
For metastatic colorectal cancer (mCRC), FOLFOX plus Bevacizumab is a top second-line treatment. For patients with RAS-mutant mCRC, FOLFIRI plus Bevacizumab and Panitumumab is recommended for better survival outcomes.
Area of Science:
- Oncology
- Clinical Pharmacology
- Biostatistics
Background:
- Optimal second-line systemic treatment for metastatic colorectal cancer (mCRC) remains unclear.
- Evidence synthesis is crucial for guiding clinical decisions in advanced cancer care.
Purpose of the Study:
- To systematically compare the efficacy and safety of various second-line systemic treatments for mCRC.
- To identify the optimal treatment strategies based on patient subgroups, including RAS gene status.
Main Methods:
- A comprehensive literature search was conducted across major databases (PubMed, Web of Science, EMBASE, Cochrane Library) up to February 2024.
- A network meta-analysis (NMA) using Markov Chain Monte Carlo (MCMC) techniques was employed to analyze progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and adverse events (AEs).
- Surface Under the Cumulative Ranking Curve (SUCRA) was used to rank treatments, with subgroup analyses performed for RAS gene status.
Main Results:
- 47 randomized controlled trials (RCTs) involving 16,925 patients and 44 treatments were analyzed.
- FOLFOX + Bevacizumab + Erlotinib showed superiority in improving overall survival (OS SUCRA: 92.7%).
- Irinotecan + CMAB009 demonstrated an advantage in progression-free survival (PFS SUCRA: 86.4%), while FOLFIRI + Trebananib excelled in overall response rate (ORR SUCRA: 88.1%).
- FOLFOX + Bevacizumab showed favorable outcomes in PFS, OS, ORR, and partial response (PR) with comparable safety.
- In RAS-mutant populations, FOLFIRI + Bevacizumab + Panitumumab was superior for OS (87.9%) and PFS (70.2%).
- In RAS-wild-type populations, FOLFIRI + Bevacizumab significantly improved OS (73.2%) and PFS (65.1%).
Conclusions:
- FOLFOX + Bevacizumab is suggested as a potentially optimal second-line systemic treatment for the majority of mCRC patients.
- FOLFIRI + Bevacizumab + Panitumumab is recommended for RAS-mutant mCRC populations.
- Treatment decisions should consider individual patient physiological status and clinical context.
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