PMID- 35530323
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Acceptability of Drugs in the Treatment of Unresectable/Metastatic BRAF 
      V600-Mutant Melanoma: A Systematic Review and Network Meta-Analysis.
PG  - 865656
LID - 10.3389/fonc.2022.865656 [doi]
LID - 865656
AB  - BACKGROUND: Although many novel regimens have entered the treatment paradigm for 
      unresectable/metastatic BRAF V600-mutant melanoma, there is still a lack of 
      head-to-head comparison in terms of security. We conducted a network 
      meta-analysis to compare the risk of adverse events (AEs) across different 
      treatments and to provide an acceptability ranking for patients. METHODS: A 
      systematic literature review was conducted in Embase, PubMed, WHO International 
      Clinical Trials Registry Platform, and Clinical Trials.gov with a time frame from 
      database inception to December 24, 2021. We retrieved evidence on the cumulative 
      incidence of any-grade AEs means grades 1-5 AEs (regardless of severity) and 
      severe AEs based on the pooled risk ratios (RRs) and 95% credible intervals (95% 
      CrI). RESULTS: Twelve publications and thirteen treatments enrolling 5,803 
      patients were included. For any-grade AEs, the acceptability of combined 
      dabrafenib and trametinib is superior to the combination of vemurafenib and 
      cobimetinib (RR: 0.94; Crl: 0.89, 0.98). Furthermore, nivolumab combined with 
      ipilimumab increases any-grade AEs than single-agent ipilimumab (RR: 0.90; Crl: 
      0.83, 0.96) or nivolumab (RR: 0.90; Crl: 0.84, 0.97). For severe AEs, dabrafenib 
      has the best acceptability than single-agent vemurafenib (RR: 0.66; Crl: 0.50, 
      0.87) or encorafenib (RR: 0.64; Crl: 0.43, 0.94). In addition, ipilimumab (SUCRA: 
      0.87) ranks first in the acceptability for any-grade AEs, and nivolumab (SUCRA: 
      0.95) ranks first in the acceptability for severe AEs. The ranking of the 
      combination of vemurafenib and cobimetinib (SUCRA: 0.66) is superior to 
      encorafenib in combination with binimetinib (SUCRA: 0.39) and combination of 
      vemurafenib and cobimetinib (SUCRA: 0.18). CONCLUSIONS: We identified the lowest 
      AE risk treatment options for BRAF V600-mutant melanoma patients. In general, 
      immunotherapy (ipilimumab or nivolumab) has better acceptability than most 
      targeted therapies, and triplet therapies are related with the worst 
      acceptability. Moreover, single-agent dabrafenib can be used as the first choice 
      in monotherapy, and the combination of dabrafenib and trametinib is the preferred 
      combination therapy. Overall, the combination of immunotherapy drugs increases 
      any-grade and severe AEs than a single agent, whereas the condition of targeted 
      therapy drugs cannot be simply generalized. Therefore, this information can 
      facilitate evidence-based decision-making and support optimizing treatment and 
      outcomes in clinical practice.
CI  - Copyright (c) 2022 Hong, Huang, Zheng, Ye, Zhao, Wang and Shao.
FAU - Hong, Ling
AU  - Hong L
AD  - College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 
      China.
AD  - Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang 
      Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical 
      College), Hangzhou, China.
FAU - Huang, Ping
AU  - Huang P
AD  - Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang 
      Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical 
      College), Hangzhou, China.
FAU - Zheng, Xiaochun
AU  - Zheng X
AD  - Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang 
      Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical 
      College), Hangzhou, China.
FAU - Ye, Xiaolan
AU  - Ye X
AD  - Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang 
      Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical 
      College), Hangzhou, China.
FAU - Zhao, Hongying
AU  - Zhao H
AD  - Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang 
      Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical 
      College), Hangzhou, China.
FAU - Wang, Jianwei
AU  - Wang J
AD  - College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 
      China.
FAU - Shao, Yanfei
AU  - Shao Y
AD  - College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 
      China.
AD  - Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang 
      Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical 
      College), Hangzhou, China.
LA  - eng
PT  - Systematic Review
DEP - 20220421
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9068943
OTO - NOTNLM
OT  - BRAF mutation melanoma
OT  - combination therapy
OT  - immunotherapy
OT  - monotherapy
OT  - network meta-analysis
OT  - targeted therapy
OT  - toxicity
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- 2022/05/10 06:00
MHDA- 2022/05/10 06:01
PMCR- 2022/01/01
CRDT- 2022/05/09 04:21
PHST- 2022/01/30 00:00 [received]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/05/09 04:21 [entrez]
PHST- 2022/05/10 06:00 [pubmed]
PHST- 2022/05/10 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.865656 [doi]
PST - epublish
SO  - Front Oncol. 2022 Apr 21;12:865656. doi: 10.3389/fonc.2022.865656. eCollection 
      2022.