PMID- 34195094
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Triple Combination Therapy With PD-1/PD-L1, BRAF, and MEK Inhibitor for Stage 
      III-IV Melanoma: A Systematic Review and Meta-Analysis.
PG  - 693655
LID - 10.3389/fonc.2021.693655 [doi]
LID - 693655
AB  - Triple combination of anti-PD-1/PD-L1 immunotherapy and anti-BRAF plus anti-MEK 
      targeted therapy is a promising antitumor strategy and is increasingly being used 
      in clinical trials. To evaluate the safety and efficacy of triple combination of 
      PD-1/PD-L1, BRAF, and MEK inhibition in patients diagnosed with stage III-IV 
      melanoma, we performed a systematic review and meta-analysis of randomized 
      controlled trials (RCTs). The PubMed, EMBASE, and Cochrane Library were searched 
      for all studies published from inception to January 2021. The progression free 
      survival (PFS), overall survival (OS), overall response rate (ORR), and risk of 
      adverse events (AEs) were extracted by two independent investigators and pooled 
      hazard ratio (HR) or risk ratio (RR) with 95% CI were determined using the 
      random-effects model for data synthesis. Overall, five randomized controlled 
      trials encompassing 1,266 patients with stage III-IV melanoma were selected. 
      Triple combination therapy significantly improved PFS (HR = 0.71; 95% CI = 0.59 
      to 0.86; P = 0.0005) and 2-year OS (RR = 1.12; 95% CI = 1.03 to 1.23; P = 0.01), 
      but had no impact on ORR (RR = 1.09; 95% CI = 0.91 to 1.30; P = 0.37) when 
      compared with controlled treatment group. In addition, triple combination therapy 
      was associated with increased risks of hypothyroidism, arthralgia, myalgia, ALT 
      increased, AST increased, asthenia, and pyrexia compared with control group. 
      Triple combination therapy of PD-1/PD-L1, BRAF, and MEK inhibition achieved 
      better survival benefits but had higher incidence of some adverse events over 
      two-drug combination or monotherapy. Further randomized controlled clinical 
      trials are needed to verify our results. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 
      2021 CRD42021235845 Available from 
      https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235845.
CI  - Copyright (c) 2021 Liu, Zhang, Wang and Cui.
FAU - Liu, Ye
AU  - Liu Y
AD  - School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
FAU - Zhang, Xilan
AU  - Zhang X
AD  - Department of Pathology, The Second People's Hospital of Dongying, Dongying, 
      China.
FAU - Wang, Guoying
AU  - Wang G
AD  - Department of Oncology, The Second People's Hospital of Dongying, Dongying, 
      China.
FAU - Cui, Xinchang
AU  - Cui X
AD  - Department of Oncology, The Second People's Hospital of Dongying, Dongying, 
      China.
LA  - eng
PT  - Systematic Review
DEP - 20210614
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8236832
OTO - NOTNLM
OT  - BRAF inhibition
OT  - MEK inhibition
OT  - PD-1/PD-L1
OT  - melanoma
OT  - meta-analysis
OT  - triple combination therapy
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- 2021/07/02 06:00
MHDA- 2021/07/02 06:01
PMCR- 2021/01/01
CRDT- 2021/07/01 07:02
PHST- 2021/04/11 00:00 [received]
PHST- 2021/05/17 00:00 [accepted]
PHST- 2021/07/01 07:02 [entrez]
PHST- 2021/07/02 06:00 [pubmed]
PHST- 2021/07/02 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.693655 [doi]
PST - epublish
SO  - Front Oncol. 2021 Jun 14;11:693655. doi: 10.3389/fonc.2021.693655. eCollection 
      2021.