Acquired resistance to the ALK inhibitor crizotinib in the absence of an ALK mutation

  • Costa D
  • Kobayashi S
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Abstract

A review. The article presents a case of anaplastic lymphoma kinase (ALK)-translocated non-small cell lung cancer (NSCLC) with acquired resistance to crizotinib without presence of ALK kinase domain mutations in two post-progression specimens. The patient is a 61-yr-old white man with a prior 9 pack-year history of smoking and stage IV E13;A20 EML4-ALK-translocated NSCLC achieved a partial response to crizotinib 250 mg twice daily as part of clin. trial A8081001 (NCT00585195). After 8 mo of therapy, new liver metastases and a growing pleural effusion were detected. Tissue sampling of both areas confirmed NSCLC with adenocarcinoma histol. Crizotinib was discontinued and the patient died of tumor-related progression 10 mo from his first dose of crizotinib. Sequence of the cDNA from the postprogression liver and pleural specimens confirmed E13;A20 EML4-ALK. [on SciFinder(R)]

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