Background: For metastatic colorectal cancer (mCRC) patients whose disease is refractory to standard therapies, treatment with regorafenib, fruquintinib, or trifluridine/tipiracil (FTD/TPI; also known as TAS-102) with or without bevacizumab is recommended. Recent clinical trial evidence indicates that FTD/TPI + bevacizumab has superior efficacy to FTD/TPI for these patients, although its relative efficacy compared with other treatment regimens requires further evidence. Objectives: A systematic literature review (SLR) and network meta-analysis (NMA) were performed to evaluate the relative efficacy of treatments for patients with refractory mCRC. Design: SLR and NMA. Data sources and methods: Databases were searched for clinical trials evaluating treatments for refractory mCRC patients. NMA using random- and fixed-effects models was performed to estimate the relative treatment effects of FTD/TPI + bevacizumab compared with other treatment regimens on overall survival (OS) and progression-free survival (PFS). Results: Twenty-eight randomized controlled trials evaluating treatment regimens in patients with refractory mCRC were identified. Of these, 16 trials connected in a network with FTD/TPI + bevacizumab. NMA including these trials using random-effects models showed that the efficacy of FTD/TPI + bevacizumab was statistically favorable relative to that of other treatment regimens including placebo/best supportive care (hazard ratio (95% credible interval); OS: 0.41 (0.28, 0.58), PFS: 0.21 (0.14, 0.31)), FTD/TPI monotherapy (OS: 0.59 (0.43, 0.79), PFS: 0.46 (0.34, 0.64)), cetuximab (OS: 0.47 (0.29, 0.73), PFS: 0.32 (0.20, 0.53)), cetuximab + irinotecan (PFS: 0.43 (0.19, 0.98), panitumumab (OS: 0.46 (0.28, 0.72), PFS: 0.35 (0.22, 0.59)), regorafenib (OS: 0.60 (0.38, 0.95), PFS: 0.49 (0.31, 0.84)), and fruquintinib (OS: 0.62 (0.39, 0.94)). Conclusion: NMA results suggest that FTD/TPI + bevacizumab confers clinically relevant improvements in OS and PFS compared with other treatment regimens for refractory mCRC patients, supporting the use of this combination therapy in the third-line treatment setting.
Taı̈eb et al. (Thu,) studied this question.