Abstract PR008: Landscape of actionable mutations and outcomes in metastatic non-small cell lung cancer across age, sex, and race
Authors: Qian David C. , Steuer Conor E. , Tian Sibo , Carlisle Jennifer W. , Leal Ticiana A. , Behera Madhusmita , Bradley Jeffrey D. , Ramalingam Suresh S. , Higgins Kristin A. 
Published: January 2023

Abstract
Introduction: Lung cancer is the leading cause of cancer-related death due to frequent diagnosis at an advanced stage, especially among underserved populations. Given the marked heterogeneity in disease course for metastatic non-small cell lung cancer (mNSCLC), we sought to further explore its distribution of genomic alterations and outcomes across population subgroups. Methods: Clinicogenomics data were downloaded from the MSK-MET cohort study, one of the largest publicly accessible databases of metastatic cancer featuring 25775 patients in the February 2022 release. Tumor mutation burden (TMB) was quantified as number of non-synonymous mutations per megabase (Mb) sequenced. Categorical variables were compared using the χ2-test. Analysis of overall survival (OS) was performed using Cox proportional hazards regression. Results: Between 2013 and 2020, tumor and matched-normal samples from 4710 adult patients (58% female) with mNSCLC (86% adenocarcinoma) were obtained for genomic characterization. Median age at diagnosis was 67 years (IQR 59–73) and median OS was 38 months (95% CI 34–40 months). Smoking status and treatment history were unavailable. Patients self-identified as non-Hispanic white (76%), Asian (10%), Black (5%), Hispanic (4%), Native American (1%), or none of the above (1%). Compared to patients of other races, Hispanic patients were more likely to be diagnosed with mNSCLC prior to age 50 (17% vs. 7%, P&lt;0.001); Asian patients had a higher frequency of EGFR mutations (56% vs. 22%, P&lt;0.001), lower frequency of KRAS mutations (11% vs. 32%, P&lt;0.001), and longer OS (HR 0.84, 95% CI 0.72–0.98, P=0.026); Black patients had greater TMB (9% vs. 5% with ≥20 mutations per Mb, P=0.019). Every actionable mutation was more common in non-squamous cell carcinoma (SCC) than SCC, except ROS1 fusions (4% vs. 7%, P&lt;0.001). Across and within each race group, men were more likely to possess no actionable mutations compared to women (29% [range 22–67%] vs. 16% [range 5–20%], P&lt;0.05). In multivariable analysis, male sex, diagnosis earlier than age 50 or later than age 70, non-adenocarcinoma histology, greater TMB, and absence of actionable mutations involving EGFR, ALK, MET, or RET were independently associated with worse OS (P&lt;0.05). Conclusions: In this large clinicogenomic analysis of mNSCLC, men were more likely to have no actionable mutations and worse OS. Diagnosis prior to age 50 (most common among Hispanic patients) and greater TMB (most common among Black patients) also independently conferred worse OS. These findings highlight the wide heterogeneity of molecular features and outcomes in mNSCLC across age, sex, and race, underscoring the need to further individualize workup and management.
Citation Format: David C. Qian, Conor E. Steuer, Sibo Tian, Jennifer W. Carlisle, Ticiana A. Leal, Madhusmita Behera, Jeffrey D. Bradley, Suresh S. Ramalingam, Kristin A. Higgins. Landscape of actionable mutations and outcomes in metastatic non-small cell lung cancer across age, sex, and race [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR008.