Distribution of EML4-ALK fusion variants and clinical outcomes in patients with resected non-small cell lung cancer

Objectives: The molecular profiles and prognosis of anaplastic lymphoma kinase (ALK) fusion and resectable non-small cell lung cancer (NSCLC) remain unclear. This study aimed to explore the distribution of ALK fusion variants and prognostic factors in patients with surgically resected NSCLC. Conclusions: This study illustrated the patterns of EML4-ALK fusion variants and gene profiles in patients with resected NSCLC. Advanced T stage and EML4-ALK variant 3 were associated with worse prognosis. The role of TP53 mutations in prognosis is worthy of further study. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.09.012

Authors: Hong Tao, Liang Shi, Aoxue Zhou, Hongxia Li, Fei Gai, Zhan Huang, Nanying Che, Zhe Liu

Case StudyKirk SmithSeptember 24, 2020Coexisting mutation, EML4-ALK fusion, Prognosis, Resected NSCLC, Variant

EML4-ALK Fusion Subtype Is Associated with Therapeutic Efficacy in Advanced Non-Small Cell Lung Cancer

Background: The aim of this study was to investigate the molecular characteristics of each subtype of the EML4-ALK fusion gene and to evaluate the efficacy of first-line crizotinib or pemetrexed in combination with platinum in the treatment of patients with advanced NSL4-ALK fusion subtypes of advanced NSCLC. Conclusion: Among all ALK fusion subtypes, E13:A20 subtype (V1 variants) is the most common. Smoking history was a factor affecting crizotinib PFS. Compared with chemotherapy, patients with E20:A20 subtype (V2 variant) showed significant benefit with crizotinib. The median PFS of the pemetrexed combined with platinum regimen was lower than that of the E13:A20 subtype. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.08.1830

Authors: H. Wang, H. Li, J. Ma, X. Yan, P. Li, M. Zhang, X. Zhang, G. Zhang, Z. Ma

Conference PaperKirk SmithOctober 1, 2019EML4-ALK fusion gene, Non-Small Cell Lung Cancer, Variant

Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer

Advanced anaplastic lymphoma kinase (ALK) fusion-positive non–small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result of acquired resistance. Emerging data suggest that the ALK fusion variant may affect clinical outcome, but the molecular basis for this association is unknown. We identified 129 patients with ALK-positive NSCLC with known ALK variants. ALK resistance mutations and clinical outcomes on ALK TKIs were retrospectively evaluated according to ALK variant. A Foundation Medicine data set of 577 patients with ALK-positive NSCLC was also examined. Specific ALK variants may be associated with the development of ALK resistance mutations, particularly G1202R, and provide a molecular link between variant and clinical outcome. ALK variant thus represents a potentially important factor in the selection of next-generation ALK inhibitors. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2017.76.2294

Authors: Lin JJ, Zhu VW, Yoda S, Yeap BY, Schrock AB, Dagogo-Jack I, Jessop NA, Jiang GY, Le LP, Gowen K, Stephens PJ, Ross JS, Ali SM, Miller VA, Johnson ML, Lovly CM, Hata AN, Gainor JF, Iafrate AJ, Shaw AT, Ou SI