Repotrectinib’s Clinical Benefit and Its Brain Penetration in a Patient with Meningeal Carcinomatosis from G2032R-Mutated ROS-1 Positive Non-Small Cell Lung Cancer

Abstract

In this work, we report on a clinically significant response of meningeal carcinomatosis to repotrectinib in a woman with a heavily pretreated ROS1-rearranged non-small cell lung cancer (NSCLC) that harbored the concomitant solvent front G2032R mutation. Meningeal carcinomatosis has a higher incidence in oncogene addicted NSCLC due to increased life expectancy, yet no report has ever documented the activity of repotrectinib in this context. In line with its activity, we documented the presence of the drug at potentially active concentrations in the cerebrospinal fluid. Nevertheless, the short-lived response reported by our patient highlights the importance for novel ROS1-tyrosine kinase inhibitors (TKIs) to be specifically developed to be able to penetrate the blood–brain barrier.

Promising Combinatorial Therapeutic Strategies against Non-Small Cell Lung Cancer

“…Targeted therapy with Crizotinib was approved for the first time worldwide for ROS1 fusion tumors. However, several studies have documented that central nervous system (CNS) metastases developed in approximately 40% of the patients after treatment with ROS-1 fusion inhibitors [ 39 ]. New generation inhibitors (ensartinib, entrectinib, lorlatinib, repotrectinib, and taletrectinib) have been discovered after the development of resistance to crizotinib in NSCLC patients ( Table 3 ), and they have better brain penetration [ 40 ].…”