PMID- 31749704
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231019
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - Antitumor Activity and Treatment-Related Toxicity Associated With Nivolumab Plus 
      Ipilimumab in Advanced Malignancies: A Systematic Review and Meta-Analysis.
PG  - 1300
LID - 10.3389/fphar.2019.01300 [doi]
LID - 1300
AB  - Combining immune checkpoint inhibitors has shown its efficacy compared to 
      monotherapy in advanced malignancies. We conducted this meta-analysis to provide 
      latest evidence on the objective response rate (ORR) and incidence of 
      treatment-related high-grade adverse events (AEs) during nivolumab and ipilimumab 
      combination treatment and further explore from different drug dose level. PubMed 
      and the 2019 American Society of Clinical Oncology (ASCO) annual meeting 
      abstracts were searched for qualified clinical trials up to June 2019. Of the 23 
      clinical trials (13 from publications and 11 from ASCO abstracts) included, 2,114 
      and 2,674 patients were eligible for efficacy and safety analysis, respectively. 
      Pooled analysis suggested that the overall ORR was achieved in 34.5% [95% 
      confidence interval (CI), 29.1-40.4%] of patients. There was no significant 
      difference between nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks 
      (N3I1-Q3W) and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3-Q3W) 
      arms in ORR [30.8% vs 41%; odds ratio (OR), 0.72; 95% CI, 0.39-1.30; P = 0.275]. 
      Grade 3-4 AEs related to combination therapy occurred in 39.9% (95% CI, 
      33.5-46.7%) of patients; the most commonly reported grade 3-4 treatment-related 
      AEs were diarrhea (5.28%), colitis (3.96%) and increased alanine aminotransferase 
      (3.51%). Incidence of grade 3-4 AEs were significant lower in N3I1-Q3W arm than 
      in N1I3-Q3W arm (31.3% vs 55.9%; OR 0.52; 95% CI, 0.32-0.87; P = 0.012). 
      Treatment-related death was rare and occurred in 2.0% (95% CI, 1.5-2.7%) of 
      patients. Our comprehensive study provides more precise data on the incidence of 
      treatment-related high-grade AEs and ORR among patients receiving nivolumab and 
      ipilimumab combination regimens. Patients on the N3I1-Q3W arm had comparable ORR 
      and significantly occurred less grade 3-4 AEs than patients on the N1I3-Q3W arm. 
      Our finding is of great importance in assisting clinical trial design and 
      clinical medication choice.
CI  - Copyright (c) 2019 Xu, Tan, Ai, Zhang, Zheng, Liao, Yang and Wei.
FAU - Xu, Hang
AU  - Xu H
AD  - Department of Urology, Institute of Urology, West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - Tan, Ping
AU  - Tan P
AD  - Department of Urology, Institute of Urology, West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - Ai, Jianzhong
AU  - Ai J
AD  - Department of Urology, Institute of Urology, West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - Zhang, Shiyu
AU  - Zhang S
AD  - Department of Urology, Institute of Urology, West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - Zheng, Xiaonan
AU  - Zheng X
AD  - West China Medical School, Sichuan University, Chengdu, China.
FAU - Liao, Xinyang
AU  - Liao X
AD  - Department of Urology, Institute of Urology, West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - Yang, Lu
AU  - Yang L
AD  - Department of Urology, Institute of Urology, West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - Wei, Qiang
AU  - Wei Q
AD  - Department of Urology, Institute of Urology, West China Hospital, Sichuan 
      University, Chengdu, China.
LA  - eng
PT  - Systematic Review
DEP - 20191104
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6844121
OTO - NOTNLM
OT  - adverse events
OT  - combination
OT  - dosage
OT  - ipilimumab
OT  - nivolumab
OT  - objective response rate
EDAT- 2019/11/22 06:00
MHDA- 2019/11/22 06:01
PMCR- 2019/11/04
CRDT- 2019/11/22 06:00
PHST- 2019/06/29 00:00 [received]
PHST- 2019/10/11 00:00 [accepted]
PHST- 2019/11/22 06:00 [entrez]
PHST- 2019/11/22 06:00 [pubmed]
PHST- 2019/11/22 06:01 [medline]
PHST- 2019/11/04 00:00 [pmc-release]
AID - 10.3389/fphar.2019.01300 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Nov 4;10:1300. doi: 10.3389/fphar.2019.01300. eCollection 
      2019.