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Review
. 2025 Jan 1;26(1):308.
doi: 10.3390/ijms26010308.

EML4-ALK: Update on ALK Inhibitors

Alessandra Bearz  1 , Elisa Bertoli  1 , Brigida Stanzione  2 , Elisa De Carlo  2 , Alessandro Del Conte  1 , Martina Bortolot  2   3 , Sara Torresan  2   3 , Eleonora Berto  2 , Valentina Da Ros  2 , Giulia Maria Pelin  1 , Kelly Fassetta  2 , Silvia Rossetto  1 , Michele Spina  2
Affiliations
Review

EML4-ALK: Update on ALK Inhibitors

Alessandra Bearz et al. Int J Mol Sci. .

Abstract

Since the discovery of the first-generation ALK inhibitor, many other tyrosine kinase inhibitors have been demonstrated to be effective in the first line or further lines of treatment in patients with advanced non-small cell lung cancer with EMLA4-ALK translocation. This review traces the main milestones in the treatment of ALK-positive metastatic patients and the survival outcomes in the first-line and second-line settings with different ALK inhibitors. It presents the two options available for first-line treatment at the present time: sequencing different ALK inhibitors versus using the most potent inhibitor in front-line treatment. The efficacy outcomes of different ALK inhibitors in the first-line setting; the molecular profile of the disease, including mutation resistances and ALK variants and co-mutations; and patients' co-morbidities and inhibitor toxicities should be taken into account to address the choice of the first-line treatment, as suggested in this review.

Keywords: EMLA4-ALK; NSCLC; TKI; lung cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Timeline of FDA approval of ALK TKIs.
Figure 2
Figure 2
Median PFS of ALK TKIs in first-line setting. NR: not reached.
See this image and copyright information in PMC

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