Lorlatinib in a Patient with Meningeal Carcinomatosis – Case Report

Meningeal Involvement

Malignant infiltration of the meninges affects 4–15% of patients with solid tumors, most commonly in lung, breast, gastrointestinal tract cancers, and malignant melanoma. Carcinomatosis can occur in the spinal or intracranial sections of the meninges, or in both parts simultaneously. Therefore, the clinical picture is very diverse. The most common symptoms are headaches, visual, speech, and consciousness disorders, as well as behavioral changes, radiculopathy, motor problems, or incontinence. The condition usually progresses rapidly. Without treatment, the median survival ranges between 4 and 6 weeks. Using intrathecal chemotherapy and/or radiotherapy can prolong survival, but only by a few months.

Targeted Therapy

For tumors where a molecular pathological target has been identified, targeted therapies, especially those designed for good CNS penetration, expand treatment options. One of these drugs is lorlatinib, a 3rd generation anaplastic lymphoma kinase (ALK) inhibitor. ALK gene mutations are proven in 3–5% of non-small cell lung cancers (NSCLC). This was the case for the patient whose treatment was described by pulmonologists from a hospital in Fukui, Japan, in their case report published in the journal Medicine.

Case Description

A 55-year-old non-smoker was diagnosed with lung adenocarcinoma with ALK mutation positivity (cT3N3M1b, stage IVA). At the time of diagnosis, the patient did not have CNS metastases. In the 1st line, she was treated with alectinib (600 mg/day), to which the disease responded partially. 20 months after starting treatment, progression was confirmed, and brigatinib (180 mg/day) was administered. The best response achieved was again partial remission.

30 months after starting brigatinib treatment, the patient presented with diplopia and severe consciousness disorder. Cerebrospinal fluid examination and CNS imaging using magnetic resonance imaging (MRI) confirmed meningeal carcinomatosis in the cerebellar area. In the 3rd line of treatment, lorlatinib (100 mg/day) was administered. Neurological symptoms significantly improved, and after 3 months, the enhancing lesions on brain MRI scans completely disappeared. After 8 months of treatment, the patient was symptom-free and without disease progression.

Conclusion

Lorlatinib was developed to be highly effective in ALK-positive NSCLC after the failure of 1st and 2nd generation ALK inhibitors and to achieve optimal concentrations in the CNS. Both of these properties are highly needed in oncology practice and offer the potential for effective treatment of patients with metastatic CNS involvement.

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Sources:
1. Janků F., Petruželka L. Diagnosis and treatment of meningeal carcinomatosis in solid tumors. Czech and Slovak Neurology and Neurosurgery 2007; 70/103 (1): 23–29.
2. Nakashima K., Demura Y., Kurokawa K. et al. Successful treatment with lorlatinib in a patient with meningeal carcinomatosis of ALK-positive non-small cell lung cancer resistant to alectinib and brigatinib. Medicine (Baltimore) 2021; 100 (39): e27385, doi: 10.1097/MD.0000000000027385.