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Repotrectinib's Clinical Benefit and Its Brain Penetration in a Patient with Meningeal Carcinomatosis from
Giulio Metro1, Eleonora Gariazzo2, Silvia Costabile1
1Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Via Dottori, 1, 06156, Perugia, Italy.
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.
Insights
Repotrectinib showed clinical activity in meningeal carcinomatosis for a patient with ROS1-positive non-small cell lung cancer (NSCLC). However, the drug
Area of Science:
- Oncology
- Pharmacology
- Neurology
Background:
- Meningeal carcinomatosis (MC) is a serious complication of non-small cell lung cancer (NSCLC), particularly in patients with oncogene-driven disease.
- Increased life expectancy in oncogene-addicted NSCLC has led to a higher incidence of MC.
- Limited treatment options exist for MC in heavily pretreated NSCLC patients.
Purpose of the Study:
- To report the clinical response to repotrectinib in a patient with meningeal carcinomatosis and ROS1-rearranged NSCLC.
- To investigate the presence and concentration of repotrectinib in cerebrospinal fluid (CSF).
- To highlight the need for improved blood-brain barrier penetration of ROS1 inhibitors.
Main Methods:
- Case report of a single patient with heavily pretreated, ROS1-rearranged NSCLC and MC.
- Administration of repotrectinib.
- Analysis of CSF for repotrectinib concentrations.
- Clinical and radiological assessment of treatment response.
Main Results:
- The patient achieved a clinically significant response to repotrectinib.
- Repotrectinib was detected in the CSF at potentially active concentrations.
- The response to repotrectinib was short-lived.
Conclusions:
- Repotrectinib demonstrates activity against meningeal carcinomatosis in ROS1-rearranged NSCLC.
- Cerebrospinal fluid penetration of repotrectinib is feasible.
- Development of novel ROS1 tyrosine kinase inhibitors (TKIs) with enhanced blood-brain barrier penetration is crucial for sustained efficacy in leptomeningeal disease.
