Lorlatinib: a new treatment option for ROS1-positive lung cancer
Mené dans 12 pays sur 69 patients atteints d'un cancer du poumon non à petites cellules ROS1+ de stade avancé, cet essai de phase I/II évalue la dose maximale tolérée et l'efficacité, du point de vue de la réponse globale et de la réponse tumorale intracrânienne, du lorlatinib, un inhibiteur de tyrosine kinase de troisième génération ciblant ALK et ROS1
Chromosomal rearrangements of ROS1 occur in 1–2% of patients with non-small-cell lung cancer (NSCLC). The ROS1 tyrosine kinase inhibitor (TKI) crizotinib provides a marked clinical efficacy in TKI-naive ROS1-positive patients in clinical trials, with an overall response of 65–72% and an expected median progression-free survival of 19 months. Crizotinib is recommended in the first-line setting for ROS1-positive patients. However, the majority of crizotinib-treated ROS1-positive patients will experience disease progression. Two main mechanisms of resistance have been described: on-target mutations, the most common of which is Gly2032Arg, and progression in the CNS, which occurs in 30–50% of patients. The development of resistance to crizotinib and the scarcity of next-line treatment options represent an unmet medical need.
The Lancet Oncology , commentaire, 2018