PMID- 36408160
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221122
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Efficacy and safety of brigatinib in ALK-positive non-small cell lung cancer 
      treatment: A systematic review and meta-analysis.
PG  - 920709
LID - 10.3389/fonc.2022.920709 [doi]
LID - 920709
AB  - BACKGROUND: Brigatinib is a central nervous system-active second-generation 
      anaplastic lymphoma kinase (ALK) inhibitor that targets a broad range of ALK 
      rearrangements in patients with non-small cell lung cancer (NSCLC). The current 
      study aimed to analyze the pooled effects and adverse events of brigatinib in 
      patients with ALK-positive NSCLC. METHODS: The pooled estimates and 95% 
      confidence intervals (CI) were calculated with DerSimonian-Laird method and the 
      random effect model. RESULTS: The pooled objective response rate (ORR) and 
      disease control rate (DCR) of brigatinib were 64% (95% CI 45%-83%) and 88% (95% 
      CI 80%-96%), respectively. The pooled mPFS was 10.52 months (95% CI 7.66-13.37). 
      In the subgroup analyses by treatment line, the highest mPFS was reached in 
      first-line treatment (24.00 months, 95% CI 18.40-43.20), followed by 
      post-crizotinib second-line treatment (mPFS=16.26 months, 95% CI 12.87-19.65), 
      and second-line with any prior ALK tyrosine kinase inhibitors (mPFS=12.96 months, 
      95% CI 11.14-14.78). Among patients with any baseline brain metastases, the 
      pooled intracranial ORR (iORR) was estimated as 54% (95% CI 35%-73%) for any 
      treatment line, and 60% (95% CI 39%-81%) for first-line treatment. Intracranial 
      PFS (iPFS) reached 19.26 months (95% CI 14.82-23.70) in patients with any 
      baseline brain metastases. Creatine phosphokinase (CPK) increased (44%, 95% CI 
      26%-63%), diarrhea (37%, 95% CI 27%-48%), and nausea (28%, 95% CI 17%-39%) of any 
      grade were the most common adverse events. CONCLUSION: Brigatinib is effective in 
      the treatment of patients with ALK-positive NSCLC, particularly showing robust 
      intracranial PFS. Brigatinib used as first-line treatment yielded superior PFS 
      compared with brigatinib used as other treatment lines. These results suggested a 
      benefit of using brigatinib earlier in the patient's management. All adverse 
      events are manageable, with CPK increased and gastrointestinal reactions found to 
      be the most common types. SYSTEMATIC REVIEW REGISTRATION: 
      https://inplasy.com/inplasy-2022-3-0142/, identifier (INPLASY202230141).
CI  - Copyright (c) 2022 Xing, Hao, Zhang and Li.
FAU - Xing, Puyuan
AU  - Xing P
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, China.
FAU - Hao, Xuezhi
AU  - Hao X
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, China.
FAU - Zhang, Xin
AU  - Zhang X
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, China.
FAU - Li, Junling
AU  - Li J
AD  - Department of Medical Oncology, National Cancer Center/National Clinical Research 
      Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking 
      Union Medical College, Beijing, China.
LA  - eng
PT  - Systematic Review
DEP - 20221103
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9669367
OTO - NOTNLM
OT  - ALK-positive
OT  - adverse events
OT  - brigatinib
OT  - efficacy
OT  - non-small cell lung cancer
COIS- Dr. Junling Li has received speaker honorarium for serving on advisory board of 
      Takeda (China) International Trading Co., Ltd. The remaining 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- 2022/11/22 06:00
MHDA- 2022/11/22 06:01
PMCR- 2022/01/01
CRDT- 2022/11/21 04:47
PHST- 2022/04/15 00:00 [received]
PHST- 2022/10/05 00:00 [accepted]
PHST- 2022/11/21 04:47 [entrez]
PHST- 2022/11/22 06:00 [pubmed]
PHST- 2022/11/22 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.920709 [doi]
PST - epublish
SO  - Front Oncol. 2022 Nov 3;12:920709. doi: 10.3389/fonc.2022.920709. eCollection 
      2022.