PMID- 34820326
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220428
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Efficacy and Safety of First-Line Treatment Strategies for Anaplastic Lymphoma 
      Kinase-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis.
PG  - 754768
LID - 10.3389/fonc.2021.754768 [doi]
LID - 754768
AB  - BACKGROUND: Targeted therapies have led to significant improvement in the 
      management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small 
      cell lung cancer (NSCLC). We performed a network meta-analysis of frontline 
      treatment options of ALK-positive NSCLC to provide clinical guidance. METHODS: 
      PubMed, Embase, ClinicalTrials.gov, and international conference databases were 
      searched to identify relevant trials from inception to June 30, 2021. Phase III 
      randomized controlled trials (RCTs) comparing treatments for patients with 
      ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian 
      network meta-analysis. Eligible studies reported at least one of the following 
      clinical outcomes: progression-free survival (PFS), overall survival (OS), risk 
      of the central nervous system (CNS) progression, adverse events (AEs) of grade 
      (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for 
      primary outcome of PFS and secondary outcome of OS and risk of CNS progression 
      were obtained. A multivariate, consistency model, fixed-effects analysis was used 
      in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and 
      meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration's 
      tool. RESULTS: Nine RCTs comprising 2,484 patients were included with seven 
      treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, 
      and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors 
      (TKIs) significantly prolong PFS and reduced risk of CNS progression except for 
      ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None 
      of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. 
      Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 
      4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs. 
      CONCLUSIONS: Lorlatinib is associated with the highest PFS benefit and lowest 
      risk of CNS progression benefits for patients with advanced ALK-positive NSCLC, 
      compared with other first-line treatments, but with higher toxicity. The 
      implementation of a newer generation of ALK-TKIs in the first-line treatment of 
      ALK-positive NSCLC into current clinical practice is evolving rapidly.
CI  - Copyright (c) 2021 Peng, Lu, Xia, Hong, Selvaggi, Stebbing, Sun and Liang.
FAU - Peng, Ling
AU  - Peng L
AD  - Department of Respiratory Disease, Zhejiang Provincial People's Hospital, 
      Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
FAU - Lu, Dafeng
AU  - Lu D
AD  - School of Public Health, Nanjing Medical University, Nanjing, China.
FAU - Xia, Yang
AU  - Xia Y
AD  - Key Laboratory of Respiratory Disease of Zhejiang Province, Department of 
      Respiratory and Critical Care Medicine, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Hong, Shaodong
AU  - Hong S
AD  - Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 
      China.
FAU - Selvaggi, Giovanni
AU  - Selvaggi G
AD  - Xcovery Holdings, Palm, Beach Gardens, FL, United States.
FAU - Stebbing, Justin
AU  - Stebbing J
AD  - Division of Cancer, Department of Surgery and Cancer, Imperial College London, 
      London, United Kingdom.
FAU - Sun, Yilan
AU  - Sun Y
AD  - Department of Respiratory Disease, Zhejiang Provincial People's Hospital, 
      Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
FAU - Liang, Fei
AU  - Liang F
AD  - Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Systematic Review
DEP - 20211108
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8606689
OTO - NOTNLM
OT  - ALK
OT  - first-line
OT  - network meta-analysis
OT  - non-small cell lung cancer
OT  - tyrosine kinase inhibitor
COIS- JS, the Editor-in-Chief of Oncogene, has sat on SABs for Vaccitech, Heat 
      Biologics, Eli Lilly, Alveo Technologies, Pear Bio, Agenus, Equilibre 
      BioPharmaceuticals, Graviton Bioscience Corporation, Celltrion, Volvox, Certis 
      Oncology Solutions, Greenmantle, Zedsen, BryoLogyx, and BenevolentAI. He has 
      consulted with Lansdowne Partners and Vitruvian. He sits on the Board of 
      Directors for Xerion and BB Biotech Healthcare Trust PLC. GS is employed by, and 
      holds stock in, Xcovery Holdings, Inc. 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- 2021/11/26 06:00
MHDA- 2021/11/26 06:01
PMCR- 2021/01/01
CRDT- 2021/11/25 06:38
PHST- 2021/08/07 00:00 [received]
PHST- 2021/10/19 00:00 [accepted]
PHST- 2021/11/25 06:38 [entrez]
PHST- 2021/11/26 06:00 [pubmed]
PHST- 2021/11/26 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.754768 [doi]
PST - epublish
SO  - Front Oncol. 2021 Nov 8;11:754768. doi: 10.3389/fonc.2021.754768. eCollection 
      2021.