PMID- 32757054 OWN - NLM STAT- MEDLINE DCOM- 20210311 LR - 20240426 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 70 IP - 2 DP - 2021 Feb TI - Systemic therapy for metastatic renal cell carcinoma in the first-line setting: a systematic review and network meta-analysis. PG - 265-273 LID - 10.1007/s00262-020-02684-8 [doi] AB - PURPOSE: Management of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions. Therefore, we aimed to assess first-line therapy for mRCC and indirectly compare the efficacy and safety of currently available treatments. MATERIALS AND METHODS: Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or progression-free survival (OS/PFS) and/or adverse events (AEs) in mRCC patients were considered eligible. RESULTS: Six studies matched our eligibility criteria. For OS, pembrolizumab plus axitinib [hazard ratio (HR) 0.85, 95% credible interval (CrI) 0.73-0.98] and nivolumab plus ipilimumab (HR 0.86, 95% CrI 0.75-0.99) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably the best option based on analysis of the treatment ranking. For PFS, pembrolizumab plus axitinib (HR 0.86, 95% CrI 0.76-0.97) and avelumab plus axitinib (HR 0.85, 95% CrI 0.74-0.98) were statistically superior to sunitinib, and avelumab plus axitinib was likely to be the preferred option based on analysis of the treatment ranking, closely followed by pembrolizumab plus axitinib. Nivolumab plus ipilimumab had significantly lower rates of serious AEs than sunitinib. CONCLUSION: Pembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy-tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs. FAU - Mori, Keiichiro AU - Mori K AUID- ORCID: 0000-0002-6147-6569 AD - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. AD - Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. FAU - Mostafaei, Hadi AU - Mostafaei H AD - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. AD - Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. FAU - Miura, Noriyoshi AU - Miura N AD - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. AD - Department of Urology, Ehime University Graduate School of Medicine, Ehime, Japan. FAU - Karakiewicz, Pierre I AU - Karakiewicz PI AD - Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada. FAU - Luzzago, Stefano AU - Luzzago S AD - Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada. AD - Department of Urology, European Institute of Oncology, IRCCS, Milan, Italy. FAU - Schmidinger, Manuela AU - Schmidinger M AD - Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. FAU - Bruchbacher, Andreas AU - Bruchbacher A AD - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. AD - Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. FAU - Pradere, Benjamin AU - Pradere B AD - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. AD - Department of Urology, University Hospital of Tours, Tours, France. AD - Universite Francois Rabelais de Tours, PRES Centre Val de Loire, Tours, France. FAU - Egawa, Shin AU - Egawa S AD - Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. FAU - Shariat, Shahrokh F AU - Shariat SF AD - Department of Urology, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. shahrokh.shariat@meduriwien.ac.at. AD - Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan. shahrokh.shariat@meduriwien.ac.at. AD - Department of Urology, Weill Cornell Medical College, New York, NY, USA. shahrokh.shariat@meduriwien.ac.at. AD - Department of Urology, University of Texas Southwestern, Dallas, TX, USA. shahrokh.shariat@meduriwien.ac.at. AD - Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. shahrokh.shariat@meduriwien.ac.at. AD - Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. shahrokh.shariat@meduriwien.ac.at. AD - Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. shahrokh.shariat@meduriwien.ac.at. AD - European Association of Urology Research Foundation, Arnhem, Netherlands. shahrokh.shariat@meduriwien.ac.at. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20200805 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 SB - IM MH - Carcinoma, Renal Cell/*complications MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neoplasm Metastasis/*drug therapy PMC - PMC7889529 OTO - NOTNLM OT - First-line OT - Immune-checkpoint inhibitors OT - Network meta-analysis OT - Renal cell carcinoma COIS- None of the authors have conflicts of interest to disclose. EDAT- 2020/08/07 06:00 MHDA- 2021/03/12 06:00 PMCR- 2020/08/05 CRDT- 2020/08/07 06:00 PHST- 2020/06/08 00:00 [received] PHST- 2020/07/23 00:00 [accepted] PHST- 2020/08/07 06:00 [pubmed] PHST- 2021/03/12 06:00 [medline] PHST- 2020/08/07 06:00 [entrez] PHST- 2020/08/05 00:00 [pmc-release] AID - 10.1007/s00262-020-02684-8 [pii] AID - 2684 [pii] AID - 10.1007/s00262-020-02684-8 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2021 Feb;70(2):265-273. doi: 10.1007/s00262-020-02684-8. Epub 2020 Aug 5.