UMMS Affiliation

Department of Molecular, Cell and Cancer Biology

Publication Date


Document Type



Cancer Biology | Enzymes and Coenzymes | Hemic and Lymphatic Diseases | Neoplasms | Oncology | Therapeutics


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.


ALK inhibitor, chemotherapy, non-small-cell lung cancer, overall survival, progression-free survival

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© 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 (

DOI of Published Version



Medicina (Kaunas). 2019 Jan 29;55(2):29. doi: 10.3390/medicina55020029. Link to article on publisher's site

Journal/Book/Conference Title

Medicina (Kaunas, Lithuania)

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Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.