EML4-ALK: Update on ALK Inhibitors
Alessandra Bearz, Elisa Bertoli, Brigida Stanzione, Elisa De Carlo, Alessandro Del Conte, Martina Bortolot, Sara Torresan, Eleonora Berto, Valentina Da Ros, Giulia Maria Pelin, Kelly Fassetta, Silvia Rossetto, Michele Spina
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.