• Andrea Casadei-Gardini, Alessandro Vagheggini, Fabio Gelsomino, Andrea Spallanzani, Paola Ulivi, Giulia Orsi, Giulia Rovesti, Kalliopi Andrikou, Emiliano Tamburini, Mario Scartozzi, and Stefano Cascinu.
• Division of Oncology, Department of Oncology and Hematology, University Hospital Modena, Modena, Italy. Electronic address: casadeigardini@gmail.com.
• Clin Colorectal Cancer. 2020 Jun 1; 19 (2): 82-90.e9.

BackgroundIn the absence of head-to-head comparison studies, the present network meta-analysis evaluated and compared the efficacy of 4 therapeutic alternatives for refractory colorectal cancer.Materials And MethodsThe search focused on results from phase III randomized controlled trials. Separate (subgroup) network meta-analyses were conducted to obtain drug comparisons stratified by various patient characteristics. The principal outcome of interest was overall survival (OS).ResultsNo difference in OS was found between regorafenib and TAS-102. For a rectal primary location, TAS-102 conferred benefit versus placebo (hazard ratio [HR], 0.671), but regorafenib did not (HR, 0.950). For patients aged > 65 years, TAS-102 showed benefit versus placebo (HR, 0.579) but regorafenib did not (HR, 0.816). For patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 in the indirect comparison, regorafenib showed benefit versus placebo (HR, 0.687), as did TAS-102 (HR, 0.756) but with a lower advantage. For patients with RAS wild type not previously treated with anti-EGFR antibodies, panitumumab was the optimal choice for OS.ConclusionsNo differences in OS were found between regorafenib and TAS-102. Possible greater efficacy was found for TAS-102 compared with regorafenib for patients with a rectal primary location, ECOG PS > 0, and age > 65 years. In contrast, regorafenib showed possible greater effectiveness for patients with ECOG PS 0 and age < 65 years. In the RAS WT population, the anti-EGFR drug showed superiority with respect to TAS-102 and regorafenib. These results should be viewed as only exploratory, and further prospective studies are warranted to validate these data.Copyright © 2019 Elsevier Inc. All rights reserved.

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