AUTHOR=Li Meichen , Hou Xue , Zhou Chengzhi , Feng Weineng , Jiang Guanming , Long Hao , Yang Shuang , Chen Jing , Wang Na , Wang Kaicheng , Chen Likun 

TITLE=Prevalence and Clinical Impact of Concomitant Mutations in Anaplastic Lymphoma Kinase Rearrangement Advanced Non-small-Cell Lung Cancer (Guangdong Association of Thoracic Oncology Study 1055)

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01216

DOI=10.3389/fonc.2020.01216

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> In patients with anaplastic lymphoma kinase <italic>(ALK</italic>) rearrangement-positive advanced non–small-cell lung cancer (NSCLC), <italic>ALK</italic> inhibitors are now the standard treatment, but their clinical efficacy varies widely for each patient. In this multicenter retrospective study, we evaluated the clinical efficacy of crizotinib according to the <italic>ALK</italic> rearrangement variants and concomitant mutations present.</p><p><bold>Patients and Methods:</bold> A total 132 patients with <italic>ALK</italic> rearrangement advanced NSCLC from 4 centers in Guangdong province, China were evaluated. All patients received crizotinib treatment and their <italic>ALK</italic> rearrangement status was identified by next-generation sequencing (NGS).</p><p><bold>Results:</bold> The median progression-free survival (PFS) in patients with EML4-<italic>ALK</italic> rearrangement (<italic>n</italic> = 121), non-EML4-<italic>ALK</italic> rearrangement (<italic>n</italic> = 5), and EML4-<italic>ALK</italic> arrangement accompanied by non-EML4-<italic>ALK</italic> rearrangement (<italic>n</italic> = 6) was 12.8, 7.5, and 7.4 months, respectively, with no significant difference between them (<italic>p</italic> = 0.1554). Similarly, among patients with various EML4-<italic>ALK</italic> variants (variant 1, variant 3a/b, and other variants), the median PFS values were again comparable. According to baseline NGS data, the median PFS in patients who had <italic>ALK</italic> rearrangement only, <italic>ALK</italic> rearrangement and concomitant tumor-suppressor gene mutations, and <italic>ALK</italic> rearrangement and concomitant oncogene mutations was 14.2, 10.9, and 4.9 months, respectively; (<italic>p</italic> = 0.0002). A multivariable analysis indicated that concomitant oncogene mutations and tumor-suppressor gene mutations were both negative factors influencing the efficacy of crizotinib in <italic>ALK</italic> rearrangement NSCLC.</p><p><bold>Conclusion:</bold> Concomitant oncogene mutations and tumor-suppressor gene mutations had negative effects on the efficacy of crizotinib, while various <italic>ALK</italic> variants had a similar influence.</p>