PMID- 34733356
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220428
IS  - 1756-2872 (Print)
IS  - 1756-2880 (Electronic)
IS  - 1756-2872 (Linking)
VI  - 13
DP  - 2021 Jan-Dec
TI  - Is there a preferred first-line therapy for metastatic renal cell carcinoma? A 
      network meta-analysis.
PG  - 17562872211053189
LID - 10.1177/17562872211053189 [doi]
LID - 17562872211053189
AB  - BACKGROUND: In recent years, new therapeutic combinations based on immunotherapy 
      provided significant benefits as a first-line treatment for patients with 
      advanced renal cell carcinoma (mRCC). OBJECTIVE: This work aims to address the 
      lack of head-to-head comparisons and the uncertainty of the benefit from 
      immunotherapy-based combinations in all the International Metastatic RCC Database 
      Consortium (IMDC) subgroups. DESIGN SETTING AND PARTICIPANTS: A systematic review 
      and a network meta-analysis were performed. Overall survival (OS) in the 
      intention-to-treat (ITT) population was the primary endpoint. OS according to 
      IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 
      adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. 
      RESULTS AND LIMITATIONS: Six randomized phase III trials with 5121 patients were 
      included. There was a high likelihood (82%) that nivolumab-cabozantinib was the 
      preferred treatment in OS. The benefit of ICI-based combinations over sunitinib 
      was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best 
      risk/benefit ratio among all the ICI-based combinations. The limitations were the 
      lack of individual patient data; the heterogeneity of patients' characteristics, 
      trial designs, and follow-up times; and a limited number of studies for indirect 
      comparisons. CONCLUSIONS: A customized approach for the first-line treatment of 
      patients with mRCC should consider the risk/benefit profile of each treatment 
      option, especially considering the likeliness of long-term survival finally 
      reached in this setting.
CI  - (c) The Author(s), 2021.
FAU - Cattrini, Carlo
AU  - Cattrini C
AUID- ORCID: 0000-0003-4785-9480
AD  - Division of Oncology, University Hospital 'Maggiore della Carita', Novara, Italy.
FAU - Messina, Carlo
AU  - Messina C
AD  - Department of Oncology, A.R.N.A.S. AO Ospedale Civico Di Cristina Benfratelli, 
      Palermo, Italy.
FAU - Airoldi, Chiara
AU  - Airoldi C
AD  - Department of Translational Medicine, University of Eastern Piedmont (UPO), 
      Novara, Italy.
FAU - Buti, Sebastiano
AU  - Buti S
AD  - Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
FAU - Roviello, Giandomenico
AU  - Roviello G
AD  - Department of Health Sciences, University of Florence, Florence, Italy.
FAU - Mennitto, Alessia
AU  - Mennitto A
AD  - Division of Oncology, University Hospital 'Maggiore della Carita', Novara, Italy.
FAU - Caffo, Orazio
AU  - Caffo O
AD  - Department of Medical Oncology, Santa Chiara Hospital, Trento, Italy.
FAU - Gennari, Alessandra
AU  - Gennari A
AD  - Division of Oncology, University Hospital 'Maggiore della Carita', Novara, Italy.
FAU - Bersanelli, Melissa
AU  - Bersanelli M
AUID- ORCID: 0000-0002-6527-6281
AD  - Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, 
      Italy.
LA  - eng
PT  - Journal Article
DEP - 20211029
PL  - England
TA  - Ther Adv Urol
JT  - Therapeutic advances in urology
JID - 101487328
PMC - PMC8558789
OTO - NOTNLM
OT  - first-line
OT  - immune checkpoint inhibitors
OT  - meta-analysis
OT  - renal cell carcinoma
OT  - tyrosine kinase inhibitors
COIS- Conflict of interest statement: The authors declared the following potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article: C.C. received Travel/Accommodation/Expenses from 
      Novartis, Pfizer, Janssen, and Ipsen; advisory board from Janssen. C.M. received 
      honoraria as a speaker for scientific events from Astellas and Ipsen. S.B. 
      received honoraria as a speaker at scientific events and advisory role from 
      Bristol-Myers Squibb (BMS), Pfizer, MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca, 
      and Novartis; he also received research funding from Novartis. O.C. received 
      honoraria as advisor/speaker from Astellas, AstraZeneca, Bayer, Janssen, MSD, 
      Pfizer, and Sanofi. A.G. has declared consulting/advisory role for Roche, MSD, 
      Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; Speakers Bureau from Eisai, 
      Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and 
      Daichii Sankyo; and research funds from EISAI, Eli Lilly, and Roche. M.B. 
      received research funding from Roche S.p.A., Seqirus UK, Pfizer, Novartis, BMS, 
      Astra Zeneca, and Sanofi Genzyme; honoraria as a speaker at scientific events 
      from Bristol-Myers Squibb (BMS), Novartis, Astra Zeneca, Pierre Fabre, and 
      Pfizer; fees as a consultant for advisory role from Novartis, BMS, IPSEN, and 
      Pfizer; and fees for copyright transfer and consultancies from Sciclone 
      Pharmaceuticals. All the other authors declare no conflicts of interest.
EDAT- 2021/11/05 06:00
MHDA- 2021/11/05 06:01
PMCR- 2021/10/29
CRDT- 2021/11/04 06:23
PHST- 2021/05/13 00:00 [received]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/11/04 06:23 [entrez]
PHST- 2021/11/05 06:00 [pubmed]
PHST- 2021/11/05 06:01 [medline]
PHST- 2021/10/29 00:00 [pmc-release]
AID - 10.1177_17562872211053189 [pii]
AID - 10.1177/17562872211053189 [doi]
PST - epublish
SO  - Ther Adv Urol. 2021 Oct 29;13:17562872211053189. doi: 10.1177/17562872211053189. 
      eCollection 2021 Jan-Dec.