A novel acquired ALK F1245C mutation confers resistance to crizotinib in ALK-positive NSCLC but is sensitive to ceritinib

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Sandeep KodityalSai-Hong Ignatius Ou

Abstract

The emergence of acquired anaplastic lymphoma kinase (ALK) resistant mutations is a common molecular mechanism underpinning disease progression during crizotinib treatment of ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients. Identifying acquired resistance mutations in ALK is paramount for tailoring future therapy with second generation ALK inhibitors and beyond. Comprehensive genomic profiling using hybrid-capture next generation sequencing has been successful in identifying acquired ALK resistance mutations. Here we described the emergence of an ALK F1245C mutation in an advanced ALK+ NSCLC patient (EML4-ALK variant 3a/b) who developed slow disease progression after a durable response to crizotinib. The patient was eventually switched to ceritinib with on-going clinical response. This is the first patient report that ALK F1245C is an acquired resistance mutation to crizotinib that can be overcome by ceritinib.

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Citations

Mar 26, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Anne S TsaoHarvey I Pass
Sep 14, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Nancy K Gillis, Howard L McLeod
Jul 1, 2016·Expert Opinion on Pharmacotherapy·Yi-Chen ZhangYi-Long Wu
Aug 31, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B Hallberg, R H Palmer
Sep 1, 2017·Nature Reviews. Clinical Oncology·Alison M SchramAlexander Drilon
Nov 17, 2017·Current Treatment Options in Oncology·Xiaomin NiuHeather A Wakelee
Jul 11, 2018·Future Oncology·Claudio SiniAldo Pezzuto
Jan 21, 2018·American Journal of Hematology·Carlo Gambacorti-PasseriniTae Min Kim
Dec 15, 2016·Frontiers in Medicine·Phu N Tran, Samuel J Klempner
Sep 25, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Julia K RotowCollin M Blakely

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