Genomic profiles and treatment outcomes in young adults with stage IV non-small cell lung cancer (NSCLC): Insights from the Middle East.

Abstract

e20690 Background: NSCLCs in young adults account for less than 10% of all NSCLCs and show distinct mutational profiles compared to those in elderly patients. However, the clinical implications remain underexplored. This study aimed to evaluate the efficacy of targeted drugs for this specific NSCLC subset, providing the necessary data on their potential in personalized treatment strategies. Methods: This retrospective analysis was conducted using data between 2015 and 2023. Exclusion criteria included missing data, incomplete follow-up information, lack of histological confirmation of NSCLC diagnosis, and age > 50 years. Data on clinicopathological characteristics, genomic mutations and treatment were collected. Kaplan-Meier and Cox regression models were used to analyze survival outcomes and prognostic factors. Results: In total, 258 patients were included in the analysis. The median age was 46 years, and the majority were male (65.9%) and smokers (62.0%). Adenocarcinoma was the predominant histological type (80.6%), followed by squamous cell carcinoma (10.1%) and other histological types (9.3%). Brain metastasis at presentation was observed in 42.6% of the patients. The most prevalent actionable mutations identified were ALK (16.7%), with concurrent mutations occurring in 3.1% of the cases, predominantly ROS1 (2.7%). Other significant mutations were EGFR (13.6%), ROS1 (8.4%), and KRAS (2.4%). Analysis of first line treatments revealed that 26.0% of patients received tyrosine kinase inhibitors (TKIs). Meanwhile, 10.1% of patients were treated with combined immunotherapy and chemotherapy, 7.8% with immunotherapy alone, and 41.9% with standard chemotherapy. Patients treated with TKIs exhibited the highest 3-year overall survival (OS) rate (47.66%), followed by those receiving immunotherapy (21.0%), combined therapy (19.37%), and standard chemotherapy (9.42%). Males had a decreased 5-year OS of 13.12% compared to 21.42% in females, and patients with brain metastases showed a 5-year OS of 15.2% versus 16.25% in those without brain metastases. Patients aged 46-50 years had a 12.15% 5-year OS compared to 18.62% for those aged 40-45 years and 20.72% for those aged 21-39 years. A higher PS-ECOG score also indicated lower survival outcomes, with a 1-year OS of 8.33% for a score of 4, compared with 58.53% for scores of 0-1 and 15.86% for scores of 2-3. Multivariate Cox regression identified smoking as a poor prognostic factor (HR 1.5, 95% CI 1.1–2.2). Conclusions: While young NSCLCs with aggressive features are considered challenging, their clinical characteristics and genomic mutations suggest a distinct biological profile with benefits from novel targeted therapies. This study is the first to examine young NSCLCs patients in the Middle East, providing insights into the efficacy of precision medicine for this population.