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© 2025 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 (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
EML4-ALK: Update on ALK Inhibitors
Author
Bearz, Alessandra 1   VIAFID ORCID Logo  ; Bertoli, Elisa 1   VIAFID ORCID Logo  ; Stanzione, Brigida 2   VIAFID ORCID Logo  ; De Carlo, Elisa 2 ; Alessandro Del Conte 1   VIAFID ORCID Logo  ; Bortolot, Martina 3 ; Torresan, Sara 3   VIAFID ORCID Logo  ; Berto, Eleonora 2 ; Da Ros, Valentina 2 ; Pelin, Giulia Maria 1 ; Fassetta, Kelly 2 ; Rossetto, Silvia 1 ; Spina, Michele 2 

 Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy; [email protected] (E.B.); [email protected] (A.D.C.); [email protected] (G.M.P.); [email protected] (S.R.) 
 Centro di Riferimento Oncologico di Aviano (CRO), Department of Medical Oncology, IRCCS, 33081 Aviano, Italy; [email protected] (B.S.); [email protected] (E.D.C.); [email protected] (E.B.); [email protected] (V.D.R.); [email protected] (K.F.); [email protected] (M.S.) 
 Centro di Riferimento Oncologico di Aviano (CRO), Department of Medical Oncology, IRCCS, 33081 Aviano, Italy; [email protected] (B.S.); [email protected] (E.D.C.); [email protected] (E.B.); [email protected] (V.D.R.); [email protected] (K.F.); [email protected] (M.S.); Department of Medicine, University of Udine, 33100 Udine, Italy 
First page
308
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3153753145
Copyright
© 2025 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 (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.