PMID- 29656851 OWN - NLM STAT- MEDLINE DCOM- 20190520 LR - 20220321 IS - 1873-7560 (Electronic) IS - 0302-2838 (Linking) VI - 74 IP - 3 DP - 2018 Sep TI - First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis. PG - 309-321 LID - S0302-2838(18)30254-9 [pii] LID - 10.1016/j.eururo.2018.03.036 [doi] AB - CONTEXT: In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. OBJECTIVE: To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. EVIDENCE ACQUISITION: Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. EVIDENCE SYNTHESIS: In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. CONCLUSIONS: Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. PATIENT SUMMARY: There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation. CI - Copyright (c) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved. FAU - Wallis, Christopher J D AU - Wallis CJD AD - Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. FAU - Klaassen, Zachary AU - Klaassen Z AD - Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Department of Surgery, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: zklaassen19@gmail.com. FAU - Bhindi, Bimal AU - Bhindi B AD - Department of Urology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Ye, Xiang Y AU - Ye XY AD - MiCare Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada. FAU - Chandrasekar, Thenappan AU - Chandrasekar T AD - Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Department of Surgery, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. FAU - Farrell, Ann M AU - Farrell AM AD - Mayo Clinic Libraries, Mayo Clinic, Rochester, Minnesota, USA. FAU - Goldberg, Hanan AU - Goldberg H AD - Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Department of Surgery, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. FAU - Boorjian, Stephen A AU - Boorjian SA AD - Department of Urology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Leibovich, Bradley AU - Leibovich B AD - Department of Urology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Kulkarni, Girish S AU - Kulkarni GS AD - Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Department of Surgery, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. FAU - Shah, Prakesh S AU - Shah PS AD - Department of Paediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada. FAU - Bjarnason, Georg A AU - Bjarnason GA AD - Division of Medical Oncology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. FAU - Heng, Daniel Y C AU - Heng DYC AD - Department of Oncology, University of Calgary, Calgary, Alberta, Canada. FAU - Satkunasivam, Raj AU - Satkunasivam R AD - Department of Urology and Center for Outcomes Research, Houston Methodist Hospital, Houston, Texas, USA. FAU - Finelli, Antonio AU - Finelli A AD - Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Department of Surgery, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20180413 PL - Switzerland TA - Eur Urol JT - European urology JID - 7512719 RN - 0 (Anilides) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Ipilimumab) RN - 0 (Pyridines) RN - 1C39JW444G (cabozantinib) RN - 31YO63LBSN (Nivolumab) SB - IM CIN - Eur Urol. 2018 Sep;74(3):322-323. PMID: 29801664 CIN - Transl Cancer Res. 2019 Feb;8(1):7-10. PMID: 35116727 MH - Adult MH - Aged MH - Aged, 80 and over MH - Anilides/therapeutic use MH - Antineoplastic Agents, Immunological/adverse effects/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Renal Cell/*drug therapy/mortality/secondary MH - Female MH - Humans MH - Ipilimumab/therapeutic use MH - Kidney Neoplasms/*drug therapy/mortality/pathology MH - Male MH - Middle Aged MH - Nivolumab/therapeutic use MH - Progression-Free Survival MH - Pyridines/therapeutic use MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Cabozantinib OT - Disease-free survival OT - Network meta-analysis OT - Nivolumab OT - Renal cell carcinoma EDAT- 2018/04/17 06:00 MHDA- 2019/05/21 06:00 CRDT- 2018/04/17 06:00 PHST- 2018/02/21 00:00 [received] PHST- 2018/03/28 00:00 [accepted] PHST- 2018/04/17 06:00 [pubmed] PHST- 2019/05/21 06:00 [medline] PHST- 2018/04/17 06:00 [entrez] AID - S0302-2838(18)30254-9 [pii] AID - 10.1016/j.eururo.2018.03.036 [doi] PST - ppublish SO - Eur Urol. 2018 Sep;74(3):309-321. doi: 10.1016/j.eururo.2018.03.036. Epub 2018 Apr 13.