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

Overview

Journal Curr Oncol

Publisher MDPI

Specialty Oncology

Date 2023 May 26

PMID 37232842

Authors

Gianluca Spitaleri

Pamela Trillo Aliaga

Ilaria Attili

Ester Del Signore

Carla Corvaja

Chiara Corti

Edoardo Crimini

Antonio Passaro

Filippo de Marinis

Affiliations

Soon will be listed here.

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.

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