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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00880

The Impact of Clinical Factors, ALK Fusion Variants and BIM Polymorphism on Crizotinib-treated Advanced EML4-ALK Rearranged Non-small Cell Lung Cancer

 Yen-Ting Lin1, 2, Yi‐Nan Liu2 and  Jin-Yuan Shih1, 2*
  • 1Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan
  • 2National Taiwan University Hospital, Taiwan

Patients’ clinical factors and genetics factors such as anaplastic lymphoma kinase (ALK) fusion variants and BIM (Bcl-2-like 11) polymorphism were reported to be associated with clinical outcome in crizotinib-treated advanced non-small cell lung cancer (NSCLC). However, the results were still controversial. We analyzed outcome of 54 patients with known ALK fusion variants who received crizotinib for advanced NSCLC. 30 of them had successful BIM polymorphism analysis and 6 (20%) had a BIM deletion. Multivariate Cox regression analysis found that previous anticancer therapy (adjusted hazard ratio [aHR] 1.35, 95% CI, 1.04 – 1.76 for each additional line of therapy, p = 0.025) and Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (aHR 8.35, 95% CI, 1.52 – 45.94, p = 0.015) were independent factors for progression-free survival (PFS). Only ECOG performance status ≥ 2 (aHR 7.20, 95% CI, 1.27 – 40.79, p = 0.026) was an independent factor for overall survival (OS). Neither ALK fusion variants nor the presence of a BIM deletion was associated with crizotinib PFS or OS. After adjusted with clinical factors, different ALK variants and BIM polymorphism might not be independent factors for crizotinib PFS or OS in advanced NSCLC with ALK rearrangement.

Keywords: Non-small cell lung cancer, ALK, ALK variant, Bim, crizotinib

Received: 03 Jun 2019; Accepted: 27 Aug 2019.

Copyright: © 2019 Lin, Liu and Shih. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jin-Yuan Shih, National Taiwan University Hospital, Taipei, Taiwan,