Common Mutations in Chinese Patients With NSCLC Linked With Treatment Outcomes, Disease Severity

The frequency of several mutations that inhibit response to tyrosine kinase inhibitors and tend to lead to increased disease severity was elevated in Chinese patients with non-small cell lung cancer.

Chinese patients with non-small cell lung cancer (NSCLC) exhibited increased frequency of several mutations that may affect the efficacy of tyrosine kinase inhibitors and increase tumor mutation burden. Findings were published in Frontiers in Oncology.

Serving as the most common type of lung cancer, NSCLC is a highly heterogeneous disease with a diversity of phenotypes and genotypes in different populations. Leveraging these actionable driver alterations, identified via comprehensive genomic profiling (CGP), has greatly prolonged the survival time of patients with NSCLC.

However, researchers noted that population reports focused on Europe, America, South Korea, and China have shown differences in the frequency of driver genes among patients, which affect the efficacy of targeted drugs.

To investigate the genomic profiles of lung adenocarcinoma (LUAD) in eastern Chinese patients and their significance in targeted therapies, researchers enrolled 101 patients with diagnosed LUAD (median age, 61 years) from Zhongshan Hospital Affiliated to Fudan University between January 2018 to March 2021. Common and uncommon oncogenic alterations among participants were detected via CGP (next-generation sequencing).

Of the study cohort, 46.5% were diagnosed with stage 1, 16.8% with stage 2, 4.0% with stage 3, and 32.7% with stage 4 LUAD. A total of 71 patients had actionable mutations detected in tissues, of which 35 received targeted therapies, authors said. Efficacy of targeted drugs was examined in the 32 patients who provided follow-up information.

In total, 314 mutated genes were detected via CGP, with the most commonly mutated genes being epidermal growth factor receptor (EGFR) (53%) and tumor protein p53 (TP53) (32%), whereas the less frequently mutated genes were erb-b2 receptor tyrosine kinase 2 (ERBB2) (25%), ATR serine/threonine kinase (ATR) (20%), CCAAT enhancer binding protein alpha (CEBPA) (16%), RB transcriptional corepressor 1 (RB1) (16%), transcription factor 7 like 2 (TCF7L2) (14%), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) (12%), and spectrin alpha, erythrocytic 1 (SPTA1) (12%).

The frequency of ERBB2, ATR, CEBPA, RB1 and TCF7L2 mutations in the Chinese patient cohort was found to be much higher than that in the databases. Moreover, CEBPA mutations were noted to affect the efficacy of EGFR-tyrosine kinase inhibitors, with ERBB2, CEBPA, and TCF7L2 mutated tumors tending to have higher tumor mutation burden.

“Patients with LUAD from eastern China have a unique profile of mutations,” concluded the study authors. “The targeted DNA panel is helpful for personalized treatment decisions of patients with LUAD, and specific mutations may affect the efficacy of targeted therapies.”

Reference

Liu J, Xu W, Ye M, Liu Z, and Li C. Genetic alteration profiling of Chinese lung adenocarcinoma and its effect on targeted therapy efficacy. Front Oncol. Published online December 14, 2021. doi:10.3389/fonc.2021.726547