PMID- 34722290
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Balancing the Risk-Benefit Ratio of Immune Checkpoint Inhibitor and Anti-VEGF 
      Combination Therapy in Renal Cell Carcinoma: A Systematic Review and 
      Meta-Analysis.
PG  - 739263
LID - 10.3389/fonc.2021.739263 [doi]
LID - 739263
AB  - BACKGROUND: Although immune checkpoint inhibitors (ICIs) combined with vascular 
      endothelial growth factor receptor (VEGFR)-targeted therapy and sunitinib 
      monotherapy have been widely applied to metastatic renal cell carcinoma (mRCC), 
      effectiveness and safety data are still lacking. To optimize clinical 
      decision-making, we conducted a systematic review and meta-analysis of published 
      randomized clinical trials to characterize the efficacy and the risk of adverse 
      events (AEs) in patients treated with ICIs plus anti-VEGF therapy. MATERIALS AND 
      METHODS: We used PubMed, EMBASE, and the Cochrane Library to retrieve randomized 
      controlled trials (RCTs) published before March 27, 2021. The efficacy outcomes 
      were progression-free survival (PFS), overall survival (OS), and objective 
      response rate (ORR). The pooled risk ratio (RR) and 95% confidence intervals (CI) 
      of AEs were calculated in the safety analysis. RESULTS: Six RCTs involving 4,227 
      patients were identified after a systematic search. For OS, ICI and anti-VEGF 
      combination therapy decreased mortality approximately 30% in the 
      intention-to-treat population (ITT) (hazard ratio (HR) = 0.70, 95% CI: 
      0.57-0.87), but there was no statistical difference in patients evaluated as 
      "favorable" by the International Metastatic Renal-Cell Carcinoma Database 
      Consortium (IMDC) criteria compared with monotherapy (HR = 0.90, 95% CI: 
      0.55-1.46, p = 0.66). In terms of PFS, the progression risk for all participants 
      declined 35% (HR = 0.65, 95% CI: 0.50-0.83) and patients evaluated as "poor" by 
      IMDC benefited further (HR = 0.46, 95% CI: 0.36-0.58). No evident divergence was 
      found in age and sex subgroups. The RRs of all-grade hypertension, arthralgia, 
      rash, proteinuria, high-grade (grades 3-5) arthralgia, and proteinuria developed 
      after combination therapy were increased compared with sunitinib. The risk of 
      high-grade hypertension and rash showed no statistical difference. However, the 
      risk of hand-foot skin reaction (HFSR), stomatitis, and dysgeusia decreased in 
      combination therapy groups. CONCLUSIONS: Compared with sunitinib, OS, PFS, and 
      ORR were significantly improved in patients receiving ICI and anti-VEGF 
      combination therapy at the expense of increased specific AEs. More attention 
      should be paid to individualized application of these combination therapies to 
      achieve the best benefit-risk ratio in the clinic. SYSTEMATIC REVIEW 
      REGISTRATION: [https://inplasy.com/] INPLASY: 202130104.
CI  - Copyright (c) 2021 Tao, Zhang, An, Lan, Xu, Ge and Yao.
FAU - Tao, Li
AU  - Tao L
AD  - Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
FAU - Zhang, Huiyun
AU  - Zhang H
AD  - Department of Oncology, Beijing Chaoyang Hospital, Capital Medical University, 
      Beijing, China.
FAU - An, Guangyu
AU  - An G
AD  - Department of Oncology, Beijing Chaoyang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Lan, Haoning
AU  - Lan H
AD  - Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
FAU - Xu, Yaoqi
AU  - Xu Y
AD  - Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
FAU - Ge, Yang
AU  - Ge Y
AD  - Department of Oncology, Beijing Chaoyang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Yao, Jiannan
AU  - Yao J
AD  - Department of Oncology, Beijing Chaoyang Hospital, Capital Medical University, 
      Beijing, China.
LA  - eng
PT  - Systematic Review
DEP - 20211014
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8552014
OTO - NOTNLM
OT  - VEGF targeted therapy
OT  - combination therapy
OT  - efficacy
OT  - immune checkpoint inhibitors (ICI)
OT  - renal cell carcinoma (RCC)
OT  - safety
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- 2021/11/02 06:00
MHDA- 2021/11/02 06:01
PMCR- 2021/01/01
CRDT- 2021/11/01 09:24
PHST- 2021/07/10 00:00 [received]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/11/01 09:24 [entrez]
PHST- 2021/11/02 06:00 [pubmed]
PHST- 2021/11/02 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.739263 [doi]
PST - epublish
SO  - Front Oncol. 2021 Oct 14;11:739263. doi: 10.3389/fonc.2021.739263. eCollection 
      2021.