Efficacy and safety of TAS-102 in refractory metastatic colorectal cancer: a meta-analysis
Received 18 May 2018
Accepted for publication 4 July 2018
Published 28 August 2018 Volume 2018:10 Pages 2915—2924
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Professor Raphael Catane
Duke Chen,1,* Yu-Shen Wu,2,* Huapeng Lin,3,* Yihan Wang,1 Longhao Li,1 Tao Zhang1
1Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
*These authors contributed equally to this work
Background: TAS-102 has been applied to metastatic colorectal cancer (mCRC) patients who had received at least two prior regimens of standard chemotherapy. This meta-analysis is designed to assess the efficacy and safety of TAS-102 in patients with mCRC.
Methods: We searched randomized controlled trials (RCTs) through PubMed, Embase, Web of Science and Cochrane clinical trial databases and clinicaltrial.gov from database initiation to March 2018. The overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and incidence of adverse events were summarized with the use of hazard ratio (HR) or risk ratio (RR).
Results: Three RCTs with 1318 patients were included. Results showed that TAS-102 significantly improved OS (HR 0.70, 95% confidence interval [CI] 0.62–0.79) and PFS (HR 0.46, 95% CI 0.40–0.52) in patients who were intolerant or refractory to fluoropyrimidine, irinotecan and oxaliplatin. The pooled odds ratio of DCR was 4.15 (95% CI 3.18–5.43). Notably, there were significant OS benefits both in patients with KRAS mutation (HR 0.76, 95% CI 0.63–0.92) and those with wild-type KRAS (HR 0.66, 95% CI 0.55–0.79). These benefits were also observed in patients with different numbers of metastatic sites. However, patients with >18 months since the diagnosis of first metastases seemed to have better OS (HR 0.65, 95% CI 0.55–0.77). The most common toxicities associated with TAS-102 were neutropenia (RR 116.51, 95% CI 23.51–577.33), leucopenia (RR 67.70, 95% CI 13.63–336.29), anemia (RR 4.28, 95% CI 2.70–6.79) and diarrhea (RR 5.10, 95% CI 1.40–18.61).
Conclusion: TAS-102 significantly improves OS, PFS and DCR in refractory mCRC patients with tolerable toxicity. Meanwhile, the OS benefits have nothing to do with KRAS status and the number of metastatic sites.
Keywords: TAS-102, metastatic colorectal cancer, meta-analysis
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