ALK inhibitors for non-small cell lung cancer: A systematic review and network meta-analysis

We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included partici...

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Published inPloS one Vol. 15; no. 2; p. e0229179
Main Authors Elliott, Jesse, Bai, Zemin, Hsieh, Shu-Ching, Kelly, Shannon E, Chen, Li, Skidmore, Becky, Yousef, Said, Zheng, Carine, Stewart, David J, Wells, George A
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 19.02.2020
Public Library of Science (PLoS)
Subjects
Alectinib
Anaplastic Lymphoma Kinase - antagonists & inhibitors
Anopheles
Brigatinib
Cancer therapies
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - enzymology
Ceritinib
Chemotherapy
Clinical trials
Comparative analysis
Computer and Information Sciences
Crizotinib
Crossovers
Death
Drug therapy
Fatalities
Grey literature
Heart
Humans
Inhibitors
Kinases
Lorlatinib
Lung cancer
Lung diseases
Lung Neoplasms - drug therapy
Lung Neoplasms - enzymology
Lymphoma
Lymphomas
Medicine and Health Sciences
Meta-analysis
Methods
Mutation
Network Meta-Analysis
Non-small cell lung cancer
Non-small cell lung carcinoma
Operating systems (Software)
Physical Sciences
Prejudice
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Protein-tyrosine kinase
Research and Analysis Methods
Research methodology
Risk analysis
Risk assessment
Small cell lung cancer
Small cell lung carcinoma
Survival
Systematic review
Tumors
Web portals
Canada
United States > US
Online AccessGet full text

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Abstract We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI] -0.16 to 1.46; odds ratio 2.58 (0.76-11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95% CrI]: crizotinib 0.46 [0.39-0.54]; ceritinib 0.52 [0.42-0.64]; alectinib 300 BID 0.16 [0.08-0.33]; alectinib 600 BID 0.23 [0.17-0.30]; brigatinib 0.23 [0.15-0.35]), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 [0.17-0.70]; alectinib v. ceritinib 0.30 [0.14-0.64]; brigatinib v. crizotinib 0.49 [0.33-0.73]; brigatinib v. ceritinib 0.43 [0.27-0.70]). OS was improved with alectinib compared with chemotherapy (HR 0.57 [95% CrI 0.39-0.83]) and crizotinib (0.68 [0.48-0.96]). Use of crizotinib (odds ratio 2.08 [95% CrI 1.56-2.79]) and alectinib (1.60 [1.00-2.58]) but not ceritinib (1.25 [0.90-1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants. Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
AbstractList We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI] -0.16 to 1.46; odds ratio 2.58 (0.76-11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95% CrI]: crizotinib 0.46 [0.39-0.54]; ceritinib 0.52 [0.42-0.64]; alectinib 300 BID 0.16 [0.08-0.33]; alectinib 600 BID 0.23 [0.17-0.30]; brigatinib 0.23 [0.15-0.35]), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 [0.17-0.70]; alectinib v. ceritinib 0.30 [0.14-0.64]; brigatinib v. crizotinib 0.49 [0.33-0.73]; brigatinib v. ceritinib 0.43 [0.27-0.70]). OS was improved with alectinib compared with chemotherapy (HR 0.57 [95% CrI 0.39-0.83]) and crizotinib (0.68 [0.48-0.96]). Use of crizotinib (odds ratio 2.08 [95% CrI 1.56-2.79]) and alectinib (1.60 [1.00-2.58]) but not ceritinib (1.25 [0.90-1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants. Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
Background We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). Methods We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. Results Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI] –0.16 to 1.46; odds ratio 2.58 (0.76–11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95% CrI]: crizotinib 0.46 [0.39–0.54]; ceritinib 0.52 [0.42–0.64]; alectinib 300 BID 0.16 [0.08–0.33]; alectinib 600 BID 0.23 [0.17–0.30]; brigatinib 0.23 [0.15–0.35]), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 [0.17–0.70]; alectinib v. ceritinib 0.30 [0.14–0.64]; brigatinib v. crizotinib 0.49 [0.33–0.73]; brigatinib v. ceritinib 0.43 [0.27–0.70]). OS was improved with alectinib compared with chemotherapy (HR 0.57 [95% CrI 0.39–0.83]) and crizotinib (0.68 [0.48–0.96]). Use of crizotinib (odds ratio 2.08 [95% CrI 1.56–2.79]) and alectinib (1.60 [1.00–2.58]) but not ceritinib (1.25 [0.90–1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants. Conclusion(s) Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
BACKGROUNDWe sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). METHODSWe searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. RESULTSThirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI] -0.16 to 1.46; odds ratio 2.58 (0.76-11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95% CrI]: crizotinib 0.46 [0.39-0.54]; ceritinib 0.52 [0.42-0.64]; alectinib 300 BID 0.16 [0.08-0.33]; alectinib 600 BID 0.23 [0.17-0.30]; brigatinib 0.23 [0.15-0.35]), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 [0.17-0.70]; alectinib v. ceritinib 0.30 [0.14-0.64]; brigatinib v. crizotinib 0.49 [0.33-0.73]; brigatinib v. ceritinib 0.43 [0.27-0.70]). OS was improved with alectinib compared with chemotherapy (HR 0.57 [95% CrI 0.39-0.83]) and crizotinib (0.68 [0.48-0.96]). Use of crizotinib (odds ratio 2.08 [95% CrI 1.56-2.79]) and alectinib (1.60 [1.00-2.58]) but not ceritinib (1.25 [0.90-1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants. CONCLUSION(S)Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
Background We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). Methods We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. Results Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI] –0.16 to 1.46; odds ratio 2.58 (0.76–11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95% CrI]: crizotinib 0.46 [0.39–0.54]; ceritinib 0.52 [0.42–0.64]; alectinib 300 BID 0.16 [0.08–0.33]; alectinib 600 BID 0.23 [0.17–0.30]; brigatinib 0.23 [0.15–0.35]), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 [0.17–0.70]; alectinib v. ceritinib 0.30 [0.14–0.64]; brigatinib v. crizotinib 0.49 [0.33–0.73]; brigatinib v. ceritinib 0.43 [0.27–0.70]). OS was improved with alectinib compared with chemotherapy (HR 0.57 [95% CrI 0.39–0.83]) and crizotinib (0.68 [0.48–0.96]). Use of crizotinib (odds ratio 2.08 [95% CrI 1.56–2.79]) and alectinib (1.60 [1.00–2.58]) but not ceritinib (1.25 [0.90–1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants. Conclusion(s) Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046. Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval [CrI] -0.16 to 1.46; odds ratio 2.58 (0.76-11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio [95% CrI]: crizotinib 0.46 [0.39-0.54]; ceritinib 0.52 [0.42-0.64]; alectinib 300 BID 0.16 [0.08-0.33]; alectinib 600 BID 0.23 [0.17-0.30]; brigatinib 0.23 [0.15-0.35]), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 [0.17-0.70]; alectinib v. ceritinib 0.30 [0.14-0.64]; brigatinib v. crizotinib 0.49 [0.33-0.73]; brigatinib v. ceritinib 0.43 [0.27-0.70]). OS was improved with alectinib compared with chemotherapy (HR 0.57 [95% CrI 0.39-0.83]) and crizotinib (0.68 [0.48-0.96]). Use of crizotinib (odds ratio 2.08 [95% CrI 1.56-2.79]) and alectinib (1.60 [1.00-2.58]) but not ceritinib (1.25 [0.90-1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants. Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
Audience Academic
Author Bai, Zemin
Skidmore, Becky
Elliott, Jesse
Wells, George A
Zheng, Carine
Kelly, Shannon E
Hsieh, Shu-Ching
Chen, Li
Yousef, Said
Stewart, David J
AuthorAffiliation 1 Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
3 Division of Medical Oncology, University of Ottawa and The Ottawa Hospital, Ottawa, Canada
Laurentian University, CANADA
2 Independent Information Specialist, Ottawa, Canada
AuthorAffiliation_xml – name: Laurentian University, CANADA
– name: 2 Independent Information Specialist, Ottawa, Canada
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– name: 3 Division of Medical Oncology, University of Ottawa and The Ottawa Hospital, Ottawa, Canada
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  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
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  fullname: Bai, Zemin
  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
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  fullname: Hsieh, Shu-Ching
  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
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  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
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  fullname: Chen, Li
  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
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  fullname: Yousef, Said
  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
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  surname: Zheng
  fullname: Zheng, Carine
  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
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  surname: Wells
  fullname: Wells, George A
  organization: Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Canada
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32074131$$D View this record in MEDLINE/PubMed
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2020 Elliott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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– notice: 2020 Elliott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BS is a paid information consultant/contractor to the Ottawa Hospital Heart Institute. DS has received personal fees from Roche Canada, Beohringer Ingelheim Canada, Novartis Canada, AstraZeneca Canada, Bristol-Myers Squibb Canada, Exactis, and Pfizer Canada, as well as grants from Celgene, outside of the submitted work. None declared by any other author. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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Snippet We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). We...
Background We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer...
We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC). We...
BACKGROUNDWe sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer...
BACKGROUND:We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer...
Background We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer...
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SubjectTerms Alectinib
Anaplastic Lymphoma Kinase - antagonists & inhibitors
Anopheles
Brigatinib
Cancer therapies
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - enzymology
Ceritinib
Chemotherapy
Clinical trials
Comparative analysis
Computer and Information Sciences
Crizotinib
Crossovers
Death
Drug therapy
Fatalities
Grey literature
Heart
Humans
Inhibitors
Kinases
Lorlatinib
Lung cancer
Lung diseases
Lung Neoplasms - drug therapy
Lung Neoplasms - enzymology
Lymphoma
Lymphomas
Medicine and Health Sciences
Meta-analysis
Methods
Mutation
Network Meta-Analysis
Non-small cell lung cancer
Non-small cell lung carcinoma
Operating systems (Software)
Physical Sciences
Prejudice
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Protein-tyrosine kinase
Research and Analysis Methods
Research methodology
Risk analysis
Risk assessment
Small cell lung cancer
Small cell lung carcinoma
Survival
Systematic review
Tumors
Web portals
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Title ALK inhibitors for non-small cell lung cancer: A systematic review and network meta-analysis
URI https://www.ncbi.nlm.nih.gov/pubmed/32074131
https://www.proquest.com/docview/2358532703
https://search.proquest.com/docview/2359416565
https://pubmed.ncbi.nlm.nih.gov/PMC7029857
https://doaj.org/article/f3e44f9d18e1406e90c69d5790f71630
http://dx.doi.org/10.1371/journal.pone.0229179
Volume 15
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