First-Line Lorlatinib for ALK-Rearranged Pulmonary Large-Cell Neuroendocrine Carcinoma with Brain Metastases and Suspected Leptomeningeal Involvement: A Case Report and Literature Review.

We report a case of ALK-rearranged pulmonary large-cell neuroendocrine carcinoma (LCNEC) with brain metastases and radiologically suspected leptomeningeal involvement, successfully treated with first-line lorlatinib. A 58-year-old woman was diagnosed with LCNEC, and molecular testing revealed an EML4-ALK fusion. Lorlatinib achieved a partial response, with regression of the primary lesion, brain metastases, and suspected leptomeningeal lesions. Our literature review showed that ALK-positive LCNEC occurs more often in younger, female, and never- or light-smoking patients. In such cases, molecular testing should be actively pursued. In LCNEC harboring actionable driver alterations, molecularly guided treatment, as used for NSCLC, may be a reasonable option.