pf-06463922 and Meningeal-Carcinomatosis

Although anaplastic lymphoma kinase (ALK) inhibitors are effective treatment options for ALK-positive non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis, achieving long-term survival in patients with NSCLC with meningeal carcinomatosis resistant to ALK inhibitors is difficult. Lorlatinib, a third-generation ALK inhibitor, was designed for selective CNS penetration, and exerts potent antitumor activity against tumors resistant to first- and/or second-generation ALK inhibitors. However, there is limited information about the activity of lorlatinib in ALK inhibitor-resistant meningeal carcinomatosis. Here, we report a case of ALK-positive lung adenocarcinoma with meningeal carcinomatosis in which lorlatinib was used after resistance to alectinib and brigatinib.. A 55-year-old woman with no history of smoking presented to our hospital with a swelling on the left neck. Clinical imaging and histopathological examination revealed a tumor of adenocarcinoma histology in the left upper lung with no CNS metastasis.. The patient was diagnosed with ALK-positive lung adenocarcinoma (cT3N3M1b: stage IVA).. She received the second-generation ALK inhibitors, alectinib and brigatinib, in the first and second-line settings, respectively. However, she developed meningeal carcinomatosis. Hence, treatment with lorlatinib was initiated in the third-line setting.. The symptoms associated with meningeal carcinomatosis, such as disturbance of consciousness and diplopia, improved dramatically. At 8 months from the initiation of lorlatinib, the patient remained well without disease progression.. Lorlatinib is an effective treatment option for patient with ALK-positive NSCLC who develop meningeal carcinomatosis resistant to second-generation ALK inhibitors. Therefore, lorlatinib should be considered in such cases, even when patients exhibit serious symptoms associated with meningeal carcinomatosis.

Topics: Aminopyridines; Anaplastic Lymphoma Kinase; Carbazoles; Carcinoma, Non-Small-Cell Lung; Drug Resistance, Neoplasm; Female; Humans; Lactams; Lung Neoplasms; Meningeal Carcinomatosis; Middle Aged; Organophosphorus Compounds; Piperidines; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Pyrazoles; Pyrimidines