• Koki Nakashima, Yoshiki Demura, Kosuke Kurokawa, Toshihiro Takeda, Norihiro Jikuya, Masahiro Oi, Toshihiko Tada, Masaya Akai, and Tamotsu Ishizuka.
• Depertment of Respiratory Medicine, Japanese Red Cross Fukui Hospital, 2-4-1, Tsukimi, Fukui-shi, Fukui-ken, Japan.
• Medicine (Baltimore). 2021 Oct 1; 100 (39): e27385e27385.

RationaleAlthough 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.Patients ConcernsA 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.DiagnosesThe patient was diagnosed with ALK-positive lung adenocarcinoma (cT3N3M1b: stage IVA).InterventionsShe 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.OutcomesThe 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.LessonsLorlatinib 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.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

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