Identification of I1171N resistance mutation in ALK-positive non-small-cell lung cancer tumor sample and circulating tumor DNA. (September 2016)

• Record Type: Journal Article
• Authors: Johnson, Alison C.; Dô, Pascal; Richard, Nicolas; Dubos, Catherine; Michels, Jean Jacques; Bonneau, Jessica; Gervais, Radj
• Is Part Of: Lung cancer. Volume 99(2016)
• Page Start: 38
• Page End: 40
• Publication Date: 2016-09
• Subjects: Non-small cell lung cancer -- ALK -- Crizotinib -- Resistance mutation -- Circulating tumor DNA; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.06.010
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: ALK mutation I1171N confers resistance to crizotinib and alectinib in NSCLC. ALK mutation I1171N is detectable in both tumor biopsy and circulating tumor DNA. Ceritinib is a therapeutic alternative when ALK mutation I1171N is detected. Abstract: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitor therapy, but resistance invariably develops and can be mediated by certain secondary mutations. The detection of these mutations is useful to guide treatment decisions, but tumors are not always easily accessible to re-biopsy. We report the case of a patient with ALK-rearranged NSCLC who presented acquired resistance to crizotinib and then alectinib. Sequencing analyses of DNA from a liver metastasis biopsy sample and circulating tumor DNA both found the same I1171N ALK kinase domain mutation, known to confer resistance to certain ALK inhibitors. However, the patient then received ceritinib, a 2nd generation ALK inhibitor, and achieved another partial response. This case underlines how ALK resistance mutation detection in peripheral blood could be a reliable, safer, and less invasive alternative to tissue-based samples in NSCLC.