Metastatic Non-Myofibroblastic Sarcoma Harbouring EML4-ALK Fusion-Dramatic Response to ALK Tyrosine Kinase Inhibitors and Development of Resistance Mutations.
Cancer Rep (Hoboken)
; 7(8): e2164, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-39188081
ABSTRACT
BACKGROUND:
Anaplastic lymphoma kinase (ALK) rearrangements are rare in non-myofibroblastic sarcoma and there is limited data on the efficacy of ALK tyrosine kinase inhibitors (TKIs) and mechanisms of resistance in these patients. CASE A 58 year-old man with metastatic non-myofibroblastic sarcoma was found to have an EML4-ALK fusion on molecular sequencing. After progression on first line systemic therapy with doxorubicin, the patient received alectinib, a second generation ALK inhibitor, and had a marked clinical and radiological response. He progressed after 5 months of treatment. Repeat lung biopsy identified the emergence of an ALK I1171N resistance mutation. He was then treated with lorlatinib, again with rapid clinical improvement and significant partial radiological response. He progressed after 4 months, at which time a repeat lung biopsy identified a new ALK kinase domain mutation G1202R. The patient was subsequently treated with chemotherapy, though unfortunately died shortly after due to rapidly progressive disease.CONCLUSION:
This case report adds to a body of evidence demonstrating the potential transformative response to targeted therapy in non-lung solid organ tumours harbouring ALK fusions. This is the first description tracking the development of resistance mutations in a patient with non-myofibroblastic sarcoma and questions the utility of the presence of G1202R mutation as a marker of lorlatinib sensitivity in non-lung ALK rearranged tumours, contrary to experience in lung cancer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
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Proteínas de Fusão Oncogênica
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Resistencia a Medicamentos Antineoplásicos
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Lactamas Macrocíclicas
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Inibidores de Proteínas Quinases
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Quinase do Linfoma Anaplásico
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Lactamas
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Mutação
Limite:
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Rep (Hoboken)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA