ROS1 non-small cell lung cancer patients treatment approach

Abstract

Initially described in glioblastomas, ROS1 rearrangements have been later found in multiple tumors as NSCLC, cholangiocarcinoma, ovarian cancer, gastric cancer, colorectal cancer, angiosarcoma, inflammatory myofibroblastic tumor and spitzoid melanoma. Detection of ROS1 rearrangements identified a subgroup of patients with clinical characteristics similar to ALK-rearranged NSCLC. Since the identification of ROS1 as an oncogenic driver in NSCLC, treatment in this population has radically changed with the rising development of targeted therapy. Although ROS1-rearranged tumors only represent around 1–2% of NSCLC, impact of targeted therapy in this population makes essential to identify them. Regulatory agencies initially approved crizotinib as first ROS1 targeted treatment in 2016. Since then, development of new therapeutic agents has multiplied. Ceritinib, lorlatinib, brigatinib and entrectinib have also been tested in this population, with the approval of the last one as first line treatment in ROS1 rearranged NSCLC. Other therapeutic agents as repotrectinib are currently under investigation. Some studies have also reviewed the efficacy of other therapies as chemotherapy or immunotherapy in this specific population. Increasing interest in the biology underlying resistance mechanisms has also emerged, as well as means to improve CNS disease control. This article aims to review the different available therapies for ROS1 rearranged NSCLC patients.