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Ref Type Journal Article
PMID (38924375)
Authors Sato Y, Sato Y, Irie K, Nanjo S, Hara S, Fujiwara S, Tomii K
Title Successful intracranial response of lorlatinib after resistance with alectinib and brigatinib in patients with ALK-positive lung adenocarcinoma: Implications of CNS penetration rate of brigatinib.
Journal Vol Issue Date Pages Journal Short Title
Thoracic cancer 15 23 2024 Aug 1772-1775 Thorac Cancer
URL
Abstract Text We present the case of a 34-year-old Japanese man with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer and brain metastases. After central nervous system (CNS) disease progression with alecintib and brigatinib, treatment with lorlatinib resulted in a good intracranial response. In this case, we investigated brain penetration ratio of brigatinib using cerebrospinal fluid and paired serum samples, and the ratio was 0.012. Further, we investigated resistance mechanisms via next-generation sequencing (NGS) using lung biopsy at lung cancer diagnosis and brain biopsy sample at progressive disease of brigatinib. No apparent resistance mechanism of known ALK resistance, such as ALK mutations, amplifications, epithelial-mesenchymal transition (EMT) and bypass pathway activation were detected. Taken together, we speculate that the low CNS penetration rate of brigatinib confers CNS progression. Further studies are warranted to reveal the resistance mechanism and propose a treatment strategy for CNS progression in ALK-positive patients.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK lung adenocarcinoma sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in an intracranial response, with improvement of the metastatic brain lesions, in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20), who previously progressed on Alunbrig (brigatinib) (PMID: 38924375). 38924375