Comparison of the efficacy and safety of third-line treatments for metastatic colorectal cancer: a systematic review and network meta-analysis

Background The objective of this study is to evaluate the efficacy and safety different third-line treatment regimens for metastatic colorectal cancer (mCRC) through a comprehensive analysis network meta-analysis (NMA). Additionally, aims provide guidance on selecting appropriate systemic patients with mCRC. Methods We conducted search PubMed, Embase, Web Science, Cochrane Central Register Controlled Trials databases from January 1, 2005, May 20, 2023, include phase II/III randomized clinical trials (RCTs) treatments primary outcome assessed in NMA was median overall survival (mOS), other outcomes included progression-free (mPFS), disease control rate (DCR), grade 3 or higher adverse events (≥3AEs). Results Ultimately, nine RCTs involving five were study. Trifluridine/tipiracil (TAS-102) plus bevacizumab (hazard ratio [HR] 0.41, 95% credible interval [CrI] 0.32-0.52) found be most effective mOS compared best supportive care (BSC). TAS-102 also significantly improved mPFS BSC (HR 0.20, CrI 0.16-0.25). In terms (AEs), (RR 0.52, 0.35-0.74) had lower incidence ≥3AEs fruquintinib, but fruquintinib 1.79, 1.10-3.11) showed better improvement DCR than TAS-102. Subgroup using Bayesian surface under cumulative ranking curve (SUCRA) ranked based OS benefit. results indicated that first across age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), time initial diagnosis randomization. Conclusion TAS-102, bevacizumab, regorafenib standard dose regimen (regorafenib), dose-escalation (regorafenib 80+) all demonstrated PFS mCRC patients. However, may optimal choice Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php , CRD42023434929.