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Systematic Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00679

Second-line systemic treatment for metastatic urothelial carcinoma: a network meta-analysis of randomized phase III clinical trials

Hyun Sik Yoon1, Cheol Kwak2, Hyeon Hoe Kim2,  Hyung Suk Kim1* and Ja Hyeon Ku2*
  • 1Dongguk University Ilsan Hospital, South Korea
  • 2Seoul National University Hospital, South Korea

Purpose: We aimed to evaluate and compare relative impacts of various second-line treatments on overall survival (OS) in metastatic urothelial carcinoma (mUC).
Method: A literature search was conducted in PubMed, Embase, and the Cochrane Library for all articles published prior to December 2018 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Seven randomized controlled trials with phase III design that met study eligibility criteria were selected for final analysis. A Bayesian framework network meta-analysis (NMA) was applied to indirectly compare the effect of each treatment on OS.
Results: In NMA, atezolizumab (HR, 0.90; 95% CI, 0.57-1.40) and pembrolizumab (HR, 0.77, 95% CI, 0.48-1.20) showed no significant effect on OS improvement compared to vinflunine. Gemcitabine/paclitaxel combination (HR, 1.30; 95% CI, 0.80-1.90) and lapatinib (HR, 0.95; 95% CI, 0.57-1.60) was not significantly associated with OS improvement compared to atezolizumab and best supportive care, respectively. However, results of rankograms revealed that pembrolizumab and atezolizumab were the first and second rank therapeutic agents for OS improvement in post-platinum mUC.
Conclusions: Our NMA results are inconclusive. The optimal second-line treatment for OS improvement could not be determined because there were no significant OS differences among evaluated therapeutic agents. However, the use of immunotherapeutic agents such as atezolizumab and pembolizumab may have priority for improving OS in second-line setting of mUC. Additional clinical trials are needed to establish second-line treatment strategies after first-line systemic chemotherapy for mUC.

Keywords: Carcinoma, chemotherapy, Immunotherapy, network meta- analysis, Transitional cell cancer (TCC)

Received: 02 May 2019; Accepted: 10 Jul 2019.

Edited by:

Scott T. Tagawa, Department of Medicine, Weill Cornell Medicine, Cornell University, United States

Reviewed by:

Takeshi Yuasa, Japanese Foundation For Cancer Research, Japan
Kouji Izumi, Kanazawa University, Japan  

Copyright: © 2019 Yoon, Kwak, Kim, Kim and Ku. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Hyung Suk Kim, Dongguk University Ilsan Hospital, Goyang, Gyeonggi, South Korea, willybimish@naver.com
Mx. Ja Hyeon Ku, Seoul National University Hospital, Seoul, South Korea, kuuro70@snu.ac.kr