Abstract
Although the National Comprehensive Cancer Network and the Chinese Society of Clinical Oncology guidelines recommend comprehensive genomic profiling of lung adenocarcinoma, it has not been widely applied in Chinese hospitals. This observational study aimed to determine real-world evidence of whether comprehensive genomic profiling can benefit the survival of patients with lung cancer. We investigated the frequency of genomic alterations, treatment strategies, and clinical outcomes in 233 patients with advanced non-small cell lung carcinoma who were routinely screened using a 508-gene panel. The most prevalent drivers were mutations of EGFR (51%), KRAS (9%), PIK3CA (7%), ALK (7%), MET (6%), and BRAF (5%). Mutations in tumor suppressor genes included TP53, KEAP1, RB1, PTEN, and APC. Median overall survival (OS) was significantly shorter among patients harboring KRAS (mutant, n = 17; WT, n = 154) and TP53 (mutant, n = 103; WT n =68) mutations (11.3 vs. 24.0 months; P = 0.16 and 18.7 vs. 28.7 months; P = 0.018, respectively). The OS was longer among patients with tumors harboring EGFR (P = 0.069) and ALK (P = 0.51) mutations. Most patients (65.4%) with the driver gene-positive (EGFR, ALK, and ROS1) tumors were received TKI treatment, whereas those with driver gene wild tumors (53.1%) chose platinum-based therapy. Univariate and multivariate analyses associated a shorter OS among patients with tumors harboring concomitant TP53 and EGFR mutations. These findings provide additional evidence from real-world on the potential importance of targeted therapies as a treatment option in NSCLC patients harboring clinically actionable mutation.
Highlights
According to the guidelines of the National Comprehensive Cancer Network, molecular tests of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), B-Raf Proto-Oncogene (BRAF), mesenchymal-epithelial transition (MET), and rearranged during transfection (RET) are recommended for all non-small cell lung cancers (NSCLC) if specimens are sufficient for molecular analysis [1]
Gender Female Male Age at diagnosis, y Median Q1, Q3 Histology Adenocarcinoma Squamous cell carcinoma Stage III IV Sample type Plasma Tissue tumor mutation burden (TMB) status Low High Microsatellite instability (MSI) microsatellite stability (MSS) MSI-L Unknown Smoking history History of smoking No history of smoking Unknown Status of Survive Alive Deceased Unknown excluding 88 of other histologic types, 233 patients with NSCLC were included in the study
The TMB significantly differed between females and males, and between smokers and non-smokers (P = 0.001), but not according to age or tumor stage (Table S2)
Summary
According to the guidelines of the National Comprehensive Cancer Network, molecular tests of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), B-Raf Proto-Oncogene (BRAF), mesenchymal-epithelial transition (MET), and rearranged during transfection (RET) are recommended for all non-small cell lung cancers (NSCLC) if specimens are sufficient for molecular analysis [1]. The emergence of targeted therapy has redefined the treatment strategies of driver gene-positive advanced lung cancer [7,8,9,10] These targeted agents have been approved based on the results of randomized controlled trials (RCTs). RWSs are designed to meet clinical needs and can include most oncology patients, accelerating patient recruitment [12] This singlecenter, prospective, observational study aimed to determine the feasibility of routine molecular profiling and the clinical benefits for patients with advanced NSCLC. Genomic analysis was performed using Oseq, which is a clinical test designed to detect mutations, copy number alterations, and select gene fusions among 508 cancer-associated genes [13]. Data were statistically analyzed and figures were prepared using R 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria) with a significance level of 0.05
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