Registry of Genetic Alterations of Taiwan Non-Small Cell Lung Cancer by Comprehensive Next-Generation Sequencing: A Real-World Cohort Study-Taiwan Cooperative Oncology Group T1521.

Abstract

Tissue-based next-generation sequencing (NGS) analysis is highly recommended for patients with advanced/metastatic non-small cell lung cancer (NSCLC). We investigated a specific patient population with NSCLC that required tissue-based NGS analysis. We enrolled 500 patients with advanced/metastatic (1) epidermal growth factor receptor (<i>EGFR</i>) mutations or anaplastic large-cell lymphoma kinase (<i>ALK</i>) rearrangement-positive NSCLC who had failed at minimum one line of tyrosine kinase inhibitor (TKI) therapy, (2) <i>EGFR-/ALK</i>-negative nonsquamous, and (3) non- or light-smoker patients with squamous NSCLC who were treatment-naïve or had failed at maximum two lines of systemic treatment. These patients were divided into five cohorts. Comprehensive tissue-based NGS testing (ACTOnco+) was conducted. Cohort 1: EGFR TKI-pretreated <i>EGFR</i>-mutated population (50.0%, n = 250), cohort 2: ALK inhibitor-pretreated <i>ALK</i>-positive population (1.6%, n = 8), cohort 3: treatment-naïve <i>EGFR-/ALK</i>-negative population (28.2%, n = 141), cohort 4: pretreated <i>EGFR-/ALK</i>-negative population (16.8%, n = 84), and cohort 5: squamous cell carcinoma (3.4%, n = 17). In cohort 1, 11.2% (28/250) of the patients had <i>MET</i> amplification, 32.4% (81/250) had been treated with osimertinib, and <i>EGFR</i> C797S was detected in 6.2% (5/81) of these patients. In cohort 2, resistance ALK mutation was detected in 37.5% (3/8) of the patients. In cohorts 3 and 4, targetable genetic alterations, including <i>EGFR</i> mutation (13.3%), <i>ERBB2</i> mutation (9.3%), <i>MET</i> exon 14 skipping (5.3%), <i>KRAS</i> G12C mutation (4.4%), <i>ROS1</i> fusion (2.7%), <i>RET</i> fusion (1.8%), and <i>BRAF</i> V600E mutation (1.3%), were detected. In cohort 5, <i>MET</i> exon 14 skipping was detected in 29.4% (5/17) of the patients. This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.