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Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer

INTRODUCTION: Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in di...

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Autores principales: Costa, Rubens Barros, Costa, Ricardo L.B., Talamantes, Sarah M., Kaplan, Jason B., Bhave, Manali A., Rademaker, Alfred, Miller, Corinne, Carneiro, Benedito A., Mahalingam, Devalingam, Chae, Young Kwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955140/
https://www.ncbi.nlm.nih.gov/pubmed/29774128
http://dx.doi.org/10.18632/oncotarget.25154
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author Costa, Rubens Barros
Costa, Ricardo L.B.
Talamantes, Sarah M.
Kaplan, Jason B.
Bhave, Manali A.
Rademaker, Alfred
Miller, Corinne
Carneiro, Benedito A.
Mahalingam, Devalingam
Chae, Young Kwang
author_facet Costa, Rubens Barros
Costa, Ricardo L.B.
Talamantes, Sarah M.
Kaplan, Jason B.
Bhave, Manali A.
Rademaker, Alfred
Miller, Corinne
Carneiro, Benedito A.
Mahalingam, Devalingam
Chae, Young Kwang
author_sort Costa, Rubens Barros
collection PubMed
description INTRODUCTION: Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. MATERIALS AND METHODS: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. RESULTS: Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. CONCLUSIONS: ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs.
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spelling pubmed-59551402018-05-17 Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer Costa, Rubens Barros Costa, Ricardo L.B. Talamantes, Sarah M. Kaplan, Jason B. Bhave, Manali A. Rademaker, Alfred Miller, Corinne Carneiro, Benedito A. Mahalingam, Devalingam Chae, Young Kwang Oncotarget Meta-Analysis INTRODUCTION: Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. MATERIALS AND METHODS: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. RESULTS: Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. CONCLUSIONS: ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs. Impact Journals LLC 2018-04-24 /pmc/articles/PMC5955140/ /pubmed/29774128 http://dx.doi.org/10.18632/oncotarget.25154 Text en Copyright: © 2018 Costa et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Meta-Analysis
Costa, Rubens Barros
Costa, Ricardo L.B.
Talamantes, Sarah M.
Kaplan, Jason B.
Bhave, Manali A.
Rademaker, Alfred
Miller, Corinne
Carneiro, Benedito A.
Mahalingam, Devalingam
Chae, Young Kwang
Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer
title Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer
title_full Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer
title_fullStr Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer
title_full_unstemmed Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer
title_short Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer
title_sort systematic review and meta-analysis of selected toxicities of approved alk inhibitors in metastatic non-small cell lung cancer
topic Meta-Analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955140/
https://www.ncbi.nlm.nih.gov/pubmed/29774128
http://dx.doi.org/10.18632/oncotarget.25154
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