Meningeal “Lazarus Response” to Lorlatinib in a ROS1-Positive NSCLC Patient Progressing to Entrectinib

Abstract

Francesco Facchinetti,1,2 Antonin Levy,3,4 Samy Ammari,5 Charles Naltet,6 Pernelle Lavaud,6 Mihaela Aldea,6 Damien Vasseur,7 David Planchard,6 Benjamin Besse2,6 1Predictive Biomarkers and Novel Therapeutic Strategies in Oncology, Inserm U981, Gustave Roussy Cancer Center, Villejuif, France; 2Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; 3Department of Radiation Oncology, Institut d’Oncologie Thoracique (IOT), Gustave Roussy Cancer Center, Villejuif, France; 4INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, Villejuif, France; 5Department of Radiology, Gustave Roussy Cancer Center, Villejuif, France; 6Department of Medical Oncology, Institut d’Oncologie Thoracique (IOT), Gustave Roussy Cancer Center, Villejuif, France; 7Department of Medical Biology and Pathology, Gustave Roussy Cancer Center, Villejuif, FranceCorrespondence: Benjamin BesseDepartment of Medical Oncology, Institut d’Oncologie Thoracique (IOT), Gustave Roussy Cancer Center, Villejuif, FranceEmail [email protected]: ROS1 tyrosine kinase inhibitors (TKIs) have showed activity and efficacy in ROS1-rearranged non-small cell lung cancer (NSCLC). In the clinical practice, besides the utilization of crizotinib, less is known about the best treatment strategies involving additional, new-generation TKIs for the sequential treatment of ROS1-positive NSCLC patients.Case Presentation: A patient suffering from a ROS1-rearranged lung adenocarcinoma, after receiving cisplatin-pemetrexed chemotherapy, was treated with entrectinib, a new-generation ALK/ROS1/NTRK inhibitor. After 16 months, central nervous system (CNS) metastases appeared, without extra-cerebral disease progression. Stereotactic brain radiotherapy was performed and entrectinib was maintained, due to the global systemic disease control. Approximately one month after radiotherapy, thoracic and meningeal progressions were detected, the latter highly symptomatic with neurocognitive disorders, visual hallucinations and worsening of psycho-motor impairment. A lumbar puncture was positive for tumor cells and for an EZR-ROS1 fusion. The administration of lorlatinib (a third-generation ALK/ROS1 inhibitor) prompted an extremely rapid improvement of clinical conditions, anticipating the positive results observed at radiologic evaluation that confirmed the disease response still ongoing after nine months since treatment start.Discussion: With the expanding availability of targeted agents with differential activity on resistance mechanism and on CNS disease, choosing wisely the best treatment strategies is pivotal to assure the best clinical outcomes in oncogene-addicted NSCLC patients. Here we have reported lorlatinib reverted an almost fatal meningeal carcinomatosis developing during entrectinib in a ROS1-positive NSCLC patient.Keywords: tyrosine kinase inhibitors, TKI, central nervous system, CNS, brain, lung cancer, radiotherapy

Keywords

• tyrosine kinase inhibitors (tki)
• central nervous system (cns)
• brain
• lung cancer
• radiotherapy.