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Open AccessArticle

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

1
Department of Oncology, Tainan Hospital, Ministry of Health and Welfare, Tainan 70043, Taiwan
2
Department of Internal Medicine, National Cheng Kung University, Tainan 704, Taiwan
3
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, LRB#427, 364 Plantation Street, Worcester, MA 01605, USA
4
Department of Public Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
5
Department of Public Health, College of Public Health, China Medical University, Taichung 40402, Taiwan
*
Author to whom correspondence should be addressed.
Medicina 2019, 55(2), 29; https://doi.org/10.3390/medicina55020029
Received: 11 December 2018 / Revised: 21 January 2019 / Accepted: 23 January 2019 / Published: 29 January 2019
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Abstract

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. View Full-Text
Keywords: ALK inhibitor; chemotherapy; non-small-cell lung cancer; progression-free survival; overall survival ALK inhibitor; chemotherapy; non-small-cell lung cancer; progression-free survival; overall survival
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Lee, Y.-C.; Hsieh, C.-C.; Lee, Y.-L.; Li, C.-Y. Which Should Be Used First for ALK-Positive Non-Small-Cell Lung Cancer: Chemotherapy or Targeted Therapy? A Meta-Analysis of Five Randomized Trials. Medicina 2019, 55, 29.

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