Second Line Treatment Decision as Per Standard of Care or Foundation Medicine in Patients With Locally Advanced or Metastatic Non‐Small Cell Lung Cancer

BACKGROUND: Molecular genetic profiling is crucial for treatment choice in patients with advanced non-small cell lung cancer (NSCLC). The Lung-ONE study aimed to determine the clinical utility of comprehensive genomic profile (CGP) tests, such as FoundationOne CDx or FoundationOne Liquid, in guiding second line therapy decisions for advanced NSCLC patients in Spain. Additionally, the study sought to describe the genomic alterations found in these patients. METHODS: This national, multicenter, prospective study included adult patients diagnosed with advanced/metastatic NSCLC undergoing first line treatment with molecular diagnostic wild-type (or unknown) for at least ALK, EGFR, and ROS-1 genes under clinical practice conditions. Physicians planned their therapeutic decision for second line treatment according to the standard of care (SOC) and subsequently re-evaluated this initial decision after a Foundation One or Foundation ACT test (FMI) report was provided. Patients continue to be followed up for up to 2 years. RESULTS: The study analyzed 151 advanced NSCLC patients. The FMI report identified 542 driver mutations in actionable genes for 132 patients, including mutations in EGFR, ALK, and BRAF that were previously missed by single-gene testing as per SOC. Additional driver alterations were also detected in ERBB2/HER2, MET, and RET genes. FMI identified mutations with designated therapies in 116 patients. Consequently, clinicians identified 44 (29.1%) patients with gene alterations associated with off-label drugs, and 13 (8.6%) patients were directed toward clinical trials. CONCLUSIONS: Using FMI data, clinicians were able to direct patients toward clinical trials and to modify SOC clinical management for several NSCLC patients. These results demonstrate the benefit of FMI genomic profiling in identifying actionable driver mutations that would otherwise be missed by SOC methodology. The findings suggest that CGP is a promising and robust tool for improving personalized medicine in NSCLC treatment in Spain.