Systematic review and network meta-analyses of third-line treatments for metastatic colorectal cancer
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REVIEW – CLINICAL ONCOLOGY
Systematic review and network meta‑analyses of third‑line treatments for metastatic colorectal cancer Thomas Walter1,2 · Neil S. Hawkins3 · Richard F. Pollock4 · Fabien Colaone5 · Suki Shergill5 · Paul J. Ross6,7 Received: 24 April 2020 / Accepted: 7 July 2020 © The Author(s) 2020
Abstract Background Limited treatment options are available in chemotherapy-refractory metastatic colorectal cancer (mCRC). The objective was to conduct a systematic literature review (SLR) and exploratory network meta-analysis (NMA) to compare the tolerability and effectiveness of SIRT with Y-90 resin microspheres, regorafenib, TAS-102 (trifluridine/tipiracil), and best supportive care (BSC) as third-line treatment in patients with mCRC. Methods An SLR was conducted to identify studies comparing two or more of the treatments and reporting overall survival (OS), progression-free survival, tumor response, or adverse event (AE) incidence. An exploratory NMA was conducted to compare hazard ratios (HRs) for OS using Markov chain Monte Carlo (MCMC) techniques. Results Seven studies were identified in the SLR: two double-blind randomized-controlled trials (RCT) for each drug, one open-label RCT, and two non-randomized comparative studies for SIRT. Patient selection criteria differed between studies, with SIRT studies including patients with liver-dominant colorectal metastases. Nausea and vomiting were more frequent with TAS-102 than regorafenib or SIRT; diarrhea was more common with TAS-102 and regorafenib than SIRT. The exploratory NMA suggested that all active treatments improved OS, with HRs of 0.48 (95% CrI 0.30–0.78) for SIRT with Y-90 resin microspheres, 0.63 (0.38–1.03) for TAS-102, and 0.67 (0.40–1.08) for regorafenib each compared to BSC. Conclusions Regorafenib, TAS-102 and SIRT using Y-90 resin microspheres are more effective than BSC in third-line treatment of mCRC; however, study heterogeneity made comparisons between active treatments challenging. SIRT is a viable treatment for third-line mCRC and its favorable AE profile should be considered in the therapeutic decision-making process. Keywords Colorectal cancer · Neoplasm metastasis · Meta-analysis Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03315-6) contains supplementary material, which is available to authorized users. * Richard F. Pollock pollock@covalence‑research.com 1
Cancer Research Center of Lyon, University of Lyon, Claude Bernard University, Lyon, France
2
Service d’oncologie médicale, Hôpital E. Herriot, Hospices Civils de Lyon, Lyon, France
3
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
4
Covalence Research Ltd, 51 Hayes Grove, London SE22 8DF, UK
5
Sirtex Medical United Kingdom Ltd, London, UK
6
Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
7
Department of Oncology, King’s College Hospital NHS Foundation Trust, London, UK
Background Colorectal cancer (CRC) is the third most commo
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