Use of next-generation sequencing (NGS) to study the impact of demographic variables on prevalence of driver mutations in non-small cell lung cancer (NSCLC).

Abstract

e21030 Background: The management of NSCLC is rapidly evolving with the discovery of new driver mutations and the introduction of targeted therapies (TT). The list of targets with FDA-approved TT is estimated to cover over half of the cases of non-squamous NSCLC. The prevalence of driver mutations varies significantly depending on several demographic variables such as smoking status, race, and sex. This abstract presents data obtained from a unique, racially diverse cohort of patients in the Washington, DC metropolitan area. Methods: Retrospective review of circulating tumor DNA NGS data from 2 commercial testing companies (Guardant and Tempus) and demographic data from our health records on 66 patients with NSCLC treated at the George Washington University Medical Faculty Associates between October 2017 and November 2021 was performed. Demographic information including age, sex, race, and smoking history, as well as histology, stage at diagnosis, and driver mutations were collected. Only patients with non-squamous NSCLC and identifiable mutations were included. Results: Mean age was 67. Most patients in this cohort were female (56.1%, male 43.9%), African-American (62.1%, Caucasian 25.8%, African 9.1%, Asian 3.0%), had smoking history (former smoker 48.5%, current smoker 25.8%, never smoker 25.8%), had adenocarcinoma (78.8%, other NSCLC (not squamous cell carcinoma or adenocarcinoma) 21.2%) with advanced stage (stage 4 62.1%, stage 3 28.8%, stage 1 3.0%, unknown 6.1%). Mutations are listed as follows: KRAS 28.8% (G12C accounted for 58% of all KRAS mutations), EGFR 19.7% (exons 19 and 21 mutations such as del19 and L858R accounted for 69%), MET 9.1% (MET amplification made up 83%), Her2 3.0% (2/66), ALK 3.0% (2/66), RET 1.5% (1/66), non-targetable mutations 34.8% (23/66). A table at the end of this abstract shows the frequency of three most prevalent mutations in this cohort distinguished by race, sex, and smoking status. Conclusions: KRAS was the most prevalent driver mutation in this cohort, followed by EGFR and MET. In concordance with the existing literature, EGFR was more prevalent in non-smokers and females, while KRAS was more common among smokers. Interestingly, a larger percentage of Africans had EGFR mutations compared to African-Americans. Given the small sample size, however, a larger scale study is needed to investigate this further. These findings show that demographic factors influence the prevalence of driver mutations which can have therapeutic implications in patients with NSCLC.[Table: see text]