ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management. Unfortunately, most patients develop acquired resistance to ALK-Is that is mediated by on- and off-target mechanisms. Translational and clinical research are continuing to develop new drugs and/or combinations in order to raise the bar and further improve the results attained up to now. This review summarizes first-line randomized clinical trials of several ALK-Is and the management of brain metastases with a focus on ALK-I resistance mechanisms. The last section addresses future developments and challenges.

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running? / G. Spitaleri, P. Trillo Aliaga, I. Attili, E. Del Signore, C. Corvaja, C. Corti, E. Crimini, A. Passaro, F. de Marinis. - In: CURRENT ONCOLOGY. - ISSN 1718-7729. - 30:5(2023 May 16), pp. 5072-5092. [10.3390/curroncol30050384]

Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?

P. Trillo Aliaga
Secondo
;
C. Corti;E. Crimini;
2023

Abstract

ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management. Unfortunately, most patients develop acquired resistance to ALK-Is that is mediated by on- and off-target mechanisms. Translational and clinical research are continuing to develop new drugs and/or combinations in order to raise the bar and further improve the results attained up to now. This review summarizes first-line randomized clinical trials of several ALK-Is and the management of brain metastases with a focus on ALK-I resistance mechanisms. The last section addresses future developments and challenges.
ALK; ALK inhibitors; NSCLC; alectinib; brain metastases; brigatinib; ceritinib; ensartinib; lorlatinib; resistance mechanisms
Settore MED/06 - Oncologia Medica
16-mag-2023
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/985528
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