K-RAS mutations indicating primary resistance to crizotinib in ALK-rearranged adenocarcinomas of the lung: Report of two cases and review of the literature. (March 2016)

• Record Type: Journal Article
• Authors: Mengoli, Maria Cecilia; Barbieri, Fausto; Bertolini, Federica; Tiseo, Marcello; Rossi, Giulio
• Is Part Of: Lung cancer. Volume 93(2016)
• Page Start: 55
• Page End: 58
• Publication Date: 2016-03
• Subjects: EGFR epidermal growth factor receptor -- KRAS Kirsten rat sarcoma viral oncogene homolog -- ALK Anaplastic Lymphoma Kinase -- FISH fluorescent in situ hybridization -- IHC immunohistochemistry -- NSCLC non-small-cell lung cancer; Lung -- Adenocarcinoma -- K-RAS -- Crizotinib -- ALK -- Resistance; 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.2016.01.002
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: K-RAS and ALK alterations in NSCLC may co-exist. K-RAS mutations confer crizotinib resistance to ALK-rearranged NSCLC. K-RAS appears a strong negative predictive marker in oncogenic-driven NSCLC. Abstract: The paradigm of mutually exclusive alterations among oncogenic drivers in non-small-cell lung cancer (NSCLC) is challenged by the increasing evidence of detection of two or more driver alterations in the same tumor using highly-sensitive molecular assays. We report here two cases of ALK -rearranged adenocarcinomas harboring concomitant exon 2 K-RAS mutations (G13D and Q61H). The patients, a 49-year-old smoker man and a 59-year-old non-smoking woman, experienced a rapid disease progression and primary resistance to crizotinib. Search for similar cases in the literature reveals that concomitant K-RAS mutations and ALK rearrangement occur in a subset of NSCLC and seems to lead to resistance to crizotinib. Among 8 similar cases receiving crizotinib previously reported (4 in first line and 4 in second line), 1 had a partial response, 1 stable disease and 6 disease progression. One patient still had progression disease when switching to ceritinib. At the end, K-RAS mutations seem to represent a negative predictive marker in ALK -rearranged adenocarcinomas treated with ALK inhibitor.