PMID- 35138046
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220510
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 11
IP  - 7
DP  - 2022 Apr
TI  - Salvage nivolumab and ipilimumab after prior anti-PD-1/PD-L1 therapy in 
      metastatic renal cell carcinoma: A meta-analysis.
PG  - 1669-1677
LID - 10.1002/cam4.4587 [doi]
AB  - BACKGROUND: Salvage nivolumab and ipilimumab after prior anti-PD-1/PD-L1 therapy 
      is frequently used off-label for clear cell metastatic renal cell carcinoma 
      (mRCC). However, limited data are available to guide such therapy. We performed a 
      meta-analysis to characterize further the safety and efficacy of salvage 
      nivolumab and ipilimumab. METHODS: We conducted a systematic review in accordance 
      with PRISMA. Studies of salvage nivolumab and ipilimumab in patients with mRCC 
      published in English before June 1, 2021 were included. We also included patients 
      treated at the Ohio State University from 2012 to 2020 through a retrospective 
      chart review. The included studies were further stratified into adaptive and 
      standard groups based on their designs. We calculated objective response rate 
      (ORR) and adverse events (AEs) via pooled data and quantitative synthesis using 
      the Stata metaprop procedure. A conservative random effect model was used to 
      combine values. RESULTS: A total of 7 studies and 310 patients were included. 
      Salvage nivolumab and ipilimumab had an ORR of 14% (95% CI, 0.09-0.21) and median 
      progression-free survival ranged between 3.7 and 5.5 months. Four out of the 
      seven studies were standard design, whereas the other three studies were 
      adaptive. The ORR was numerically higher in the standard group compared with the 
      adaptive group (21% and 9-10%, respectively). The responses to salvage nivolumab 
      and ipilimumab did not correlate with the initial anti-PD-1/PD-L1 responses (odds 
      ratio = 1.45; p = 0.5). Grade >/=3 AEs occurred in 26% of the patients (95% CI, 
      0.19-0.33). There were no new safety signals observed in this study. CONCLUSION: 
      Salvage nivolumab and ipilimumab demonstrated moderate antitumor activity and a 
      manageable safety profile in patients with mRCC who had prior anti-PD-1/PD-L1 
      therapy. IMPLICATION FOR PRACTICE: Patients with metastatic renal cell carcinoma 
      have limited treatment options after progressive disease on anti-PD-1/PD-L1 
      therapy. The role of salvage nivolumab and ipilimumab in this patient population 
      is poorly defined. The studies on this highly important and clinically relevant 
      topic are limited by small sample sizes. The results from our meta-analysis 
      suggest that nivolumab and ipilimumab are feasible in the salvage setting with 
      moderate efficacy and acceptable toxicity profile. The response rates differ with 
      different treatment designs. This information will be beneficial to guide 
      clinical decision-making and accurately estimating toxicity.
CI  - (c) 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Yang, Yuanquan
AU  - Yang Y
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
FAU - Mori, Sherry V
AU  - Mori SV
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
FAU - Li, Mingjia
AU  - Li M
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
FAU - Hinkley, Megan
AU  - Hinkley M
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
FAU - Parikh, Anish B
AU  - Parikh AB
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
FAU - Collier, Katharine A
AU  - Collier KA
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
FAU - Miah, Abdul
AU  - Miah A
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
FAU - Yin, Ming
AU  - Yin M
AUID- ORCID: 0000-0001-5743-4369
AD  - Division of Medical Oncology, The Ohio State University College of Medicine, 
      Columbus, Ohio, USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20220209
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Ipilimumab)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - B7-H1 Antigen
MH  - *Carcinoma, Renal Cell/drug therapy/etiology
MH  - Humans
MH  - Ipilimumab/adverse effects
MH  - *Kidney Neoplasms/drug therapy/pathology
MH  - Nivolumab
MH  - Retrospective Studies
PMC - PMC8986145
OTO - NOTNLM
OT  - immune checkpoint inhibitor
OT  - ipilimumab
OT  - meta-analysis
OT  - nivolumab
OT  - renal cell carcinoma
OT  - salvage treatment
COIS- None of the contributing authors have any conflicts of interest, including 
      specific financial interests and relationships and affiliations relevant to the 
      subject matter or materials discussed in the manuscript.
EDAT- 2022/02/10 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/02/09
CRDT- 2022/02/09 08:44
PHST- 2021/12/14 00:00 [revised]
PHST- 2021/11/04 00:00 [received]
PHST- 2021/12/16 00:00 [accepted]
PHST- 2022/02/10 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/02/09 08:44 [entrez]
PHST- 2022/02/09 00:00 [pmc-release]
AID - CAM44587 [pii]
AID - 10.1002/cam4.4587 [doi]
PST - ppublish
SO  - Cancer Med. 2022 Apr;11(7):1669-1677. doi: 10.1002/cam4.4587. Epub 2022 Feb 9.