Expanding the Roster of ROS1 Inhibitors
Mené sur 32 patients atteints d'un cancer du poumon non à petites cellules présentant des réarrangements de ROS1, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du céritinib (durée médiane de suivi : 14 mois) après l'échec de plusieurs chimiothérapies
In 2007, oncogenic ALK and ROS1 fusion kinases were discovered in patients with non–small-cell lung cancer (NSCLC).1,2 In the decade that has followed, ALK-positive NSCLC has become a paradigm for precision medicine with three ALK-targeted therapies—crizotinib, ceritinib, and alectinib—approved by the US Food and Drug Administration and a multitude of therapeutic strategies under development.3-5 ROS1- and ALK-positive NSCLC share a number of features, including overlapping clinicopathologic characteristics, a high degree of homology between the two tyrosine kinase domains, and sensitivity to the multitargeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib.6 However, therapeutic opportunities for ROS1 are noticeably fewer than for ALK. Crizotinib is currently the only approved targeted therapy for advanced ROS1-positive NSCLC. The approval of crizotinib was based on efficacy results from a global phase I study (PROFILE 1001) that showed an objective response rate (ORR) of 72% and median progression-free survival (PFS) of 19.2 months.7 Although additional targeted therapies with ROS1 activity have been identified, treatment options for patients with ROS1-positive NSCLC are limited, particularly if patients experience treatment failure after receiving crizotinib.
Journal of Clinical Oncology , éditorial en libre accès, 2016