Early-Stage Non-Small Cell Lung Cancer: Prevalence of Actionable Alterations in a Monocentric Consecutive Cohort

Simple Summary The therapeutic scenario of early-stage (ES) non-small cell lung cancer (NSCLC) is rapidly evolving. Precision medicine, including both targeted therapy and immunotherapy, has recently entered the clinical practice of neoadjuvant and adjuvant settings. However, only a few data are available about oncogene addiction of ES tumors. In this study, we determined the prevalence of the main lung cancer actionable alterations in a consecutive monocentric cohort of ES-NSCLC. We found that the prevalence of targetable alterations was similar between ES and advanced NSCLC, with a significant enrichment in MET exon 14 skipping alterations in ES-NSCLC. Our results can support the role of a biomarker testing strategy to improve the management of ES lung cancer patients.Abstract Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have recently opened new therapeutic scenarios. However, only a few data are available about the ES-NSCLC molecular landscape and the impact of oncogene addiction on therapy definition. Here, we determined the prevalence of the main lung cancer driver alterations in a monocentric consecutive cohort. Molecular analysis was performed on 1122 cases, including 368 ES and 754 advanced NSCLC. The prevalence of actionable alterations was similar between early and advanced stages. ES-NSCLC was significantly enriched for MET exon-14 skipping alterations and presented a lower prevalence of BRAF p.(V600E) mutation. PD-L1 expression levels, evaluated according to actionable alterations, were higher in advanced than early tumors harboring EGFR, KRAS, MET alterations and gene fusions. Taken together, these results confirm the value of biomarker testing in ES-NSCLC. Although approved targeted therapies for ES-NSCLC are still limited, the identification of actionable alterations could improve patients' selection for immunotherapy, favoring the enrollment in clinical trials and allowing a faster treatment start at disease recurrence.