PMID- 33824031 OWN - NLM STAT- MEDLINE DCOM- 20220418 LR - 20220428 IS - 1873-7560 (Electronic) IS - 0302-2838 (Linking) VI - 80 IP - 6 DP - 2021 Dec TI - A Living, Interactive Systematic Review and Network Meta-analysis of First-line Treatment of Metastatic Renal Cell Carcinoma. PG - 712-723 LID - S0302-2838(21)00214-1 [pii] LID - 10.1016/j.eururo.2021.03.016 [doi] AB - CONTEXT: Identifying the most effective first-line treatment for metastatic renal cell carcinoma (mRCC) is challenging as rapidly evolving data quickly outdate the existing body of evidence, and current approaches to presenting the evidence in user-friendly formats are fraught with limitations. OBJECTIVE: To maintain living evidence for contemporary first-line treatment for previously untreated mRCC. EVIDENCE ACQUISITION: We have created a living, interactive systematic review (LISR) and network meta-analysis for first-line treatment of mRCC using data from randomized controlled trials comparing contemporary treatment options with single-agent tyrosine kinase inhibitors. We applied an advanced programming and artificial intelligence-assisted framework for evidence synthesis to create a living search strategy, facilitate screening and data extraction using a graphical user interface, automate the frequentist network meta-analysis, and display results in an interactive manner. EVIDENCE SYNTHESIS: As of October 22, 2020, the LISR includes data from 14 clinical trials. Baseline characteristics are summarized in an interactive table. The cabozantinib + nivolumab combination (CaboNivo) is ranked the highest for the overall response rate, progression-free survival, and overall survival, whereas ipilimumab + nivolumab (NivoIpi) is ranked the highest for achieving a complete response (CR). NivoIpi, and atezolizumab + bevacizumab (AteBev) were ranked highest (lowest toxicity) and CaboNivo ranked lowest for treatment-related adverse events (AEs). Network meta-analysis results are summarized as interactive tables and plots, GRADE summary-of-findings tables, and evidence maps. CONCLUSIONS: This innovative living and interactive review provides the best current evidence on the comparative effectiveness of multiple treatment options for patients with untreated mRCC. Trial-level comparisons suggest that CaboNivo is likely to cause more AEs but is ranked best for all efficacy outcomes, except NivoIpi offers the best chance of CR. Pembrolizumab + axitinib and NivoIpi are acceptable alternatives, except NivoIpi may not be preferred for patients with favorable risk. Although network meta-analysis provides rankings with statistical adjustments, there are inherent biases in cross-trial comparisons with sparse direct evidence that does not replace randomized comparisons. PATIENT SUMMARY: It is challenging to decide the best option among the several treatment combinations of immunotherapy and targeted treatments for newly diagnosed metastatic kidney cancer. We have created interactive evidence summaries of multiple treatment options that present the benefits and harms and evidence certainty for patient-important outcomes. This evidence is updated as soon as new studies are published. CI - Copyright (c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved. FAU - Riaz, Irbaz Bin AU - Riaz IB AD - Mayo Clinic, Phoenix, AZ, USA. FAU - He, Huan AU - He H AD - Mayo Clinic, Rochester, MN, USA. FAU - Ryu, Alexander J AU - Ryu AJ AD - Mayo Clinic, Rochester, MN, USA. FAU - Siddiqi, Rabbia AU - Siddiqi R AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Naqvi, Syed Arsalan Ahmed AU - Naqvi SAA AD - Dow University of Health Sciences, Karachi, Pakistan. FAU - Yao, Yuan AU - Yao Y AD - Tsinghua University, Beijing, China. FAU - Husnain, Muhammad AU - Husnain M AD - Banner University Medical Center, University of Arizona, Tucson, AZ, USA. FAU - Narasimhulu, Deepa Maheswari AU - Narasimhulu DM AD - Mayo Clinic, Rochester, MN, USA. FAU - Mathew, Jessey AU - Mathew J AD - Mayo Clinic, Rochester, MN, USA. FAU - Sipra, Qurat Ul Ain Riaz AU - Sipra QUAR AD - Banner University Medical Center, University of Arizona, Tucson, AZ, USA. FAU - Vandvik, Per Olav AU - Vandvik PO AD - Department of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway. FAU - Joseph, Richard W AU - Joseph RW AD - Mayo Clinic, Rochester, MN, USA. FAU - Liu, Hongfang AU - Liu H AD - Mayo Clinic, Rochester, MN, USA. FAU - Wang, Zhen AU - Wang Z AD - Mayo Clinic, Rochester, MN, USA. FAU - Herasevich, Vitaly AU - Herasevich V AD - Mayo Clinic, Rochester, MN, USA. FAU - Singh, Parminder AU - Singh P AD - Mayo Clinic, Phoenix, AZ, USA. FAU - Hussain, Syed A AU - Hussain SA AD - University of Sheffield Medical School, Sheffield, UK. FAU - Ho, Thai H AU - Ho TH AD - Mayo Clinic, Phoenix, AZ, USA. FAU - Bryce, Alan H AU - Bryce AH AD - Mayo Clinic, Phoenix, AZ, USA. FAU - Pagliaro, Lance C AU - Pagliaro LC AD - Mayo Clinic, Rochester, MN, USA. FAU - Murad, Mohammad H AU - Murad MH AD - Mayo Clinic, Rochester, MN, USA. Electronic address: murad.mohammad@mayo.edu. FAU - Costello, Brian A AU - Costello BA AD - Mayo Clinic, Rochester, MN, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20210403 PL - Switzerland TA - Eur Urol JT - European urology JID - 7512719 RN - 31YO63LBSN (Nivolumab) SB - IM MH - Artificial Intelligence MH - *Carcinoma, Renal Cell/secondary MH - Female MH - Humans MH - *Kidney Neoplasms/pathology MH - Male MH - Network Meta-Analysis MH - Nivolumab/therapeutic use OTO - NOTNLM OT - *Kidney cancer OT - *Living evidence OT - *Living systematic reviews OT - *Metastatic renal cell carcinoma EDAT- 2021/04/08 06:00 MHDA- 2022/04/19 06:00 CRDT- 2021/04/07 05:48 PHST- 2020/11/05 00:00 [received] PHST- 2021/03/15 00:00 [accepted] PHST- 2021/04/08 06:00 [pubmed] PHST- 2022/04/19 06:00 [medline] PHST- 2021/04/07 05:48 [entrez] AID - S0302-2838(21)00214-1 [pii] AID - 10.1016/j.eururo.2021.03.016 [doi] PST - ppublish SO - Eur Urol. 2021 Dec;80(6):712-723. doi: 10.1016/j.eururo.2021.03.016. Epub 2021 Apr 3.