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Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials

Background and objectives: Targeted therapy is widely used in the era of precision medicine. Whether the sequence in which targeted therapy and chemotherapy are performed matters, is however not known. We examined the impact of the sequential treatment of targeted therapy and chemotherapy among adva...

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Autores principales: Lee, Yen-Chien, Hsieh, Chung-Cheng, Lee, Yen-Ling, Li, Chung-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409768/
https://www.ncbi.nlm.nih.gov/pubmed/30699985
http://dx.doi.org/10.3390/medicina55020029
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author Lee, Yen-Chien
Hsieh, Chung-Cheng
Lee, Yen-Ling
Li, Chung-Yi
author_facet Lee, Yen-Chien
Hsieh, Chung-Cheng
Lee, Yen-Ling
Li, Chung-Yi
author_sort Lee, Yen-Chien
collection PubMed
description Background and objectives: Targeted therapy is widely used in the era of precision medicine. Whether the sequence in which targeted therapy and chemotherapy are performed matters, is however not known. We examined the impact of the sequential treatment of targeted therapy and chemotherapy among advanced anaplastic lymphoma kinase (ALK), non-small cell lung cancer (NSCLC) patients. Materials and Methods: Randomized controlled trials comparing the use of ALK inhibitors with chemotherapy were included in this meta-analysis. We estimated the hazard ratios (HRs) and 95% confidence intervals (CI), for progression-free survival (PFS) and overall survival (OS) from a random effects model. Two-sided statistical tests were used to determine the significance of these estimates. Results: In five eligible studies (1404 patients), ALK targeted therapy, in comparison with chemotherapy, had a significantly higher PFS (HR = 0.48; 95% CI, 0.42–0.55), but not significantly higher OS (HR = 0.88; 95% CI, 0.72–1.07). Crossover from chemotherapy to ALK inhibitors was allowed after progression in all trials. The sensitivity analysis of the use of ALK inhibitors as either the first- or second-line treatment, showed improvements in PFS but not in OS. Conclusions: Our results indicate that using targeted therapy first improved PFS, but that the sequence in which the treatments were performed did not cause a significant difference in overall survival.
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spelling pubmed-64097682019-03-25 Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials Lee, Yen-Chien Hsieh, Chung-Cheng Lee, Yen-Ling Li, Chung-Yi Medicina (Kaunas) Article Background and objectives: Targeted therapy is widely used in the era of precision medicine. Whether the sequence in which targeted therapy and chemotherapy are performed matters, is however not known. We examined the impact of the sequential treatment of targeted therapy and chemotherapy among advanced anaplastic lymphoma kinase (ALK), non-small cell lung cancer (NSCLC) patients. Materials and Methods: Randomized controlled trials comparing the use of ALK inhibitors with chemotherapy were included in this meta-analysis. We estimated the hazard ratios (HRs) and 95% confidence intervals (CI), for progression-free survival (PFS) and overall survival (OS) from a random effects model. Two-sided statistical tests were used to determine the significance of these estimates. Results: In five eligible studies (1404 patients), ALK targeted therapy, in comparison with chemotherapy, had a significantly higher PFS (HR = 0.48; 95% CI, 0.42–0.55), but not significantly higher OS (HR = 0.88; 95% CI, 0.72–1.07). Crossover from chemotherapy to ALK inhibitors was allowed after progression in all trials. The sensitivity analysis of the use of ALK inhibitors as either the first- or second-line treatment, showed improvements in PFS but not in OS. Conclusions: Our results indicate that using targeted therapy first improved PFS, but that the sequence in which the treatments were performed did not cause a significant difference in overall survival. MDPI 2019-01-29 /pmc/articles/PMC6409768/ /pubmed/30699985 http://dx.doi.org/10.3390/medicina55020029 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Yen-Chien
Hsieh, Chung-Cheng
Lee, Yen-Ling
Li, Chung-Yi
Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials
title Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials
title_full Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials
title_fullStr Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials
title_full_unstemmed Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials
title_short Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials
title_sort which should be used first for alk-positive non-small-cell lung cancer: chemotherapy or targeted therapy? a meta-analysis of five randomized trials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409768/
https://www.ncbi.nlm.nih.gov/pubmed/30699985
http://dx.doi.org/10.3390/medicina55020029
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