PMID- 33869015
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220422
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Safety and Activity of Programmed Cell Death 1 Versus Programmed Cell Death 
      Ligand 1 Inhibitors for Platinum-Resistant Urothelial Cancer: A Meta-Analysis of 
      Published Clinical Trials.
PG  - 629646
LID - 10.3389/fonc.2021.629646 [doi]
LID - 629646
AB  - BACKGROUND: Programmed death 1/ligand 1 (PD-1/L1) inhibitors have acceptable 
      antitumor activity in patients with platinum-resistant urothelial cancer (UC). 
      However, the reliability and comparability of the antitumor activity, safety 
      profiles and survival outcomes of different immune checkpoint inhibitors are 
      unknown. Our objective was to compare the clinical efficacy and safety of 
      anti-PD-1/PD-L1 therapies in platinum-resistant UC patients. METHODS: We reviewed 
      the published trials from the PubMed, Embase and Cochrane Library databases up to 
      August 2020. A well-designed mirror principle strategy to screen and pair trial 
      characteristics was used to justify indirect comparisons. The primary end point 
      was the objective response rate (ORR). The safety profile and survival outcomes 
      were also evaluated. The restricted mean survival time (RMST) up to 12 months was 
      calculated. RESULTS: Eight studies including 1,666 advanced or metastatic UC 
      patients (1,021 patients with anti-PD-L1 treatment and 645 patients with 
      anti-PD-1 treatment) met the study criteria. The ORRs of anti-PD-1 and PD-L1 
      therapy were 22% (95% CI, 18%-25%) and 15% (95% CI, 13%-17%) with all studies 
      combined. The proportions of the treated population with a confirmed objective 
      response (I(2) = 0; P = 0.966; HR, 1.60; 95% CI, 1.23-2.07; P < 0.001) and 
      disease control (I(2) = 30.6%; P = 0.229; HR, 1.35; 95% CI, 1.10-1.66; P = 0.004) 
      were higher with anti-PD-1 therapy than with anti-PD-L1 therapy. The 
      treatment-related adverse events (AEs) (I(2) = 78.3%; P = 0.003; OR, 1.09; 95% 
      CI, 0.65-1.84; P = 0.741) and grade 3-5 treatment-related AEs (I(2) = 68.5%; P = 
      0.023; OR, 1.69; 95% CI, 0.95-3.01; P = 0.074) of anti-PD-1 therapy were 
      comparable to those of anti-PD-L1 therapy. The RMST values at the 12-month 
      follow-up were 9.4 months (95% CI,: 8.8-10.0) for anti-PD-1 therapy and 9.3 
      months (95% CI, 8.8-9.7) for anti-PD-L1 therapy (z = 0.26, P = 0.794). There was 
      no significant difference between patients in the anti-PD-1 and anti-PD-L1 groups 
      (12-month overall survival (OS): 43% versus 42%, P = 0.765. I(2) = 0; P = 0.999; 
      HR, 0.95; 95% CI, 0.83-1.09; P = 0.474). CONCLUSIONS: The results of our 
      systematic comparison suggest that anti-PD-1 therapy exhibits better antitumor 
      activity than anti-PD-L1 therapy, with comparable safety profiles and survival 
      outcomes. These findings may contribute to enhanced treatment awareness in 
      patients with platinum-resistant UC.
CI  - Copyright (c) 2021 Li, Li, Lam, Cao, Han, Zhang, Fang, Xiao and Zhou.
FAU - Li, Zaishang
AU  - Li Z
AD  - Department of Urology, Shenzhen People's Hospital, The Second Clinic Medical 
      College of Jinan University, Shenzhen, China.
AD  - Department of Urology, First Affiliated Hospital of Southern University of 
      Science and Technology, Shenzhen, China.
AD  - Department of Urology, Minimally Invasive Urology of Shenzhen Research and 
      Development Center of Medical Engineering and Technology, Shenzhen, China.
FAU - Li, Xueying
AU  - Li X
AD  - Department of Oncology, The Seventh Affiliated Hospital of Sun Yat-sen 
      University, Shenzhen, China.
FAU - Lam, Wayne
AU  - Lam W
AD  - Division of Urology, Department of Surgery, Queen Mary Hospital, The University 
      of Hong Kong, Hong Kong, Hong Kong.
FAU - Cao, Yabing
AU  - Cao Y
AD  - Department of Oncology, Hospital Kiang Wu, Macau, Macau.
FAU - Han, Hui
AU  - Han H
AD  - Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
AD  - Department of Urology, State Key Laboratory of Oncology in South China, 
      Guangzhou, China.
AD  - Department of Urology, Collaborative Innovation Center of Cancer Medicine, 
      Guangzhou, China.
FAU - Zhang, Xueqi
AU  - Zhang X
AD  - Department of Urology, Shenzhen People's Hospital, The Second Clinic Medical 
      College of Jinan University, Shenzhen, China.
AD  - Department of Urology, First Affiliated Hospital of Southern University of 
      Science and Technology, Shenzhen, China.
AD  - Department of Urology, Minimally Invasive Urology of Shenzhen Research and 
      Development Center of Medical Engineering and Technology, Shenzhen, China.
FAU - Fang, Jiequn
AU  - Fang J
AD  - Department of Urology, Shenzhen People's Hospital, The Second Clinic Medical 
      College of Jinan University, Shenzhen, China.
AD  - Department of Urology, First Affiliated Hospital of Southern University of 
      Science and Technology, Shenzhen, China.
AD  - Department of Urology, Minimally Invasive Urology of Shenzhen Research and 
      Development Center of Medical Engineering and Technology, Shenzhen, China.
FAU - Xiao, Kefeng
AU  - Xiao K
AD  - Department of Urology, Shenzhen People's Hospital, The Second Clinic Medical 
      College of Jinan University, Shenzhen, China.
AD  - Department of Urology, First Affiliated Hospital of Southern University of 
      Science and Technology, Shenzhen, China.
AD  - Department of Urology, Minimally Invasive Urology of Shenzhen Research and 
      Development Center of Medical Engineering and Technology, Shenzhen, China.
FAU - Zhou, Fangjian
AU  - Zhou F
AD  - Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
AD  - Department of Urology, State Key Laboratory of Oncology in South China, 
      Guangzhou, China.
AD  - Department of Urology, Collaborative Innovation Center of Cancer Medicine, 
      Guangzhou, China.
LA  - eng
PT  - Systematic Review
DEP - 20210401
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8047637
OTO - NOTNLM
OT  - immunotherapy
OT  - programmed cell death 1 ligand
OT  - programmed cell death 1 receptor
OT  - review
OT  - urologic neoplasms
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/04/20 06:00
MHDA- 2021/04/20 06:01
PMCR- 2021/01/01
CRDT- 2021/04/19 06:32
PHST- 2020/12/15 00:00 [received]
PHST- 2021/03/09 00:00 [accepted]
PHST- 2021/04/19 06:32 [entrez]
PHST- 2021/04/20 06:00 [pubmed]
PHST- 2021/04/20 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.629646 [doi]
PST - epublish
SO  - Front Oncol. 2021 Apr 1;11:629646. doi: 10.3389/fonc.2021.629646. eCollection 
      2021.