Clinical Utility of Comprehensive Genomic Profiling for Advanced Non‐Small Cell Lung Cancer: A Single‐Center Retrospective Study

BACKGROUND: For advanced non-small cell lung cancer (NSCLC), biomarker testing using multiplex companion diagnostics has become the standard of care. However, challenges remain in detecting rare mutations and resistance mechanisms after targeted therapy. We evaluated the prevalence of druggable genetic aberrations and the clinical utility of comprehensive genomic profiling (CGP) performed after completion of standard treatment in real-world practice. METHODS: This retrospective study analyzed 108 patients with advanced or recurrent non-small cell lung cancer who underwent comprehensive genomic profiling testing between January 2019 and December 2023 at the Kanagawa Cancer Center Hospital, Japan. Profiling was conducted using the OncoGuide NCC Oncopanel System, FoundationOne, and FoundationOne Liquid companion diagnostics. RESULTS: Druggable genetic aberrations were detected in 37% of the patients, with epidermal growth factor receptor mutations being the most common. Resistance mechanisms were identified in 9 of 19 patients who underwent re-biopsy after targeted therapy. Non-smokers had a significantly higher rate of druggable mutations (55.6%) than did smokers (27.8%). Treatment based on comprehensive genomic profiling findings was recommended for 35.2% of the patients; however, only 16.6% received the suggested therapy. In a landmark survival analysis, patients who received genomically matched therapy demonstrated a trend toward prolonged overall survival compared with those who did not (log-rank p = 0.054). CONCLUSIONS: CGP testing can identify actionable mutations missed by conventional diagnostics and may provide additional therapeutic opportunities in NSCLC.