Abstract B045: The impact of smoking status on the genomic landscape of lung squamous cell carcinoma
Authors: Rock Adam , Garg Sahil , Salgia Ravi , Villaflor Victoria , Muddasani Ramya , Massarelli Erminia , Jenkins Colby 
Published: November 2024

Introduction: Molecular diagnostics have become a standard of care in determining the appropriate treatment paradigm for patients with advanced non-small cell lung cancer (NSCLC). Current guidelines indicate that histology is the most important criteria in deciding on conducting molecular testing. In lung adenocarcinoma, guidelines recommend that all patients with advanced disease undergo comprehensive molecular testing. However, the current National Comprehensive Cancer Guidelines (NCCN) suggest only consideration of molecular testing in lung squamous cell carcinoma (SCC). Despite this recommendation, numerous genomic alterations (GAs) have been observed in lung SCC including amplifications, fusions, and mutations. The list of druggable genetic alterations has been growing, now including ROS1 rearrangements, RET rearrangements, and MET alterations with associated pharmacologic therapies. This suggests a role for broader comprehensive molecular profiling in NSCLC. We sought to assess the impact of smoking status on the proportion of actionable GAs in a cohort of lung SCC patients. Methods: We retrospectively reviewed liquid biopsy reports from Guardant 360 between October 2020 and July 2023 that were obtained in the context of routine clinical care at a single institution, the City of Hope Comprehensive Cancer Center. We then obtained social history from clinical documentation. Patients were categorized based on smoking status with the following categories: non-smoker, remote smoking history (quit &gt;20 years prior), or smoking history (ongoing or quit within the last 20 year). Results: 56 patients were included in the final analysis. 98% (n = 55) patients had a documented smoking history, with 24% (n=13) classified as non-smokers. In total, 96% (n = 54) patients had detectable alterations of variable significance Of the 13 patients classified as non-smokers, 62% (n=8) patients had an actionable GA detected by liquid biopsy which has a current FDA approved agent. Of targetable GAs in the non-smoking cohort, the following alterations were observed: EGFR exon 19 deletion (44% , n=4), MET exon 14 skipping mutation (22%, n=2), EGFR G719S (11%, n=1), EGFR E114K (11% n=1). Of the 8 patients with targetable alterations detected, responses by RECIST included 4 partial response, 2 stable disease, and 2 progressive disease. The objective response rate (ORR) for this group was 55.6% and the clinical benefit rate (CBR) was 77.8%. Discussion: These data help illustrate the importance of genomic testing in lung SCC, particularly in patients with a non- smoking status. Given that 62% of non-smokers harbored a mutation treated with an FDA- approved agent, up-front genomic testing is of paramount importance. For smokers, numerous alterations were also detected which have been shown to result in decreased efficacy of immunotherapy regimens. This analysis helps highlight the potential value of liquid biopsy testing in lung SCC patients with both non-smoking and smoking histories.

Citation Format: Adam Rock, Sahil Garg, Ravi Salgia, Victoria Villaflor, Ramya Muddasani, Erminia Massarelli, Colby Jenkins. The impact of smoking status on the genomic landscape of lung squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B045.