Clinical Application of In-House Comprehensive Genomic Profiling for Thoracic Cancer: Insights From a Japanese...

Comprehensive genomic profiling (CGP) is useful for optimizing targeted therapy and immunotherapy strategies for thoracic malignancies. This study aimed to evaluate the clinical utility and diagnostic complementarity of the in-house sequencing platform Rapid-Neo. We retrospectively analyzed 110 patients with thoracic malignancies who underwent Rapid-Neo testing. The baseline characteristics, sequencing results, concordance with companion diagnostics (CDx), and clinical outcomes were assessed. Of 110 patients, 100 (90.9%) had primary lung cancer. Rapid-Neo identified at least one genomic alteration in 99.1% of cases and well-established driver alterations in 66.0% of lung cancer cases. TMB-high and MSI-high statuses were observed in 9.0% and 2.0% of cases, respectively. Among the 90 cases with prior CDx, Rapid-Neo identified driver alterations in 10.0% of the cases, including EGFR, KRAS, MET, RET, and ERBB2, suggesting its potential to overcome the limitations of conventional CDx tests. High concordance (96.8%) was observed between the Rapid-Neo and CDx results, finally. In EGFR-mutant lung adenocarcinoma, high tumor mutation burden (TMB) was associated with a significantly shorter progression-free survival (PFS) after EGFR-TKI therapy (HR = 2.58, p = 0.018) and remained an independent prognostic factor in multivariate analysis. Furthermore, among patients receiving immune checkpoint inhibitors (ICIs), favorable genomic markers such as TMB-high or MSI-high were associated with prolonged PFS. Rapid-Neo demonstrated high sensitivity and concordance with CDx, while also identifying actionable driver alterations missed by the initial CDx. Moreover, the genomic markers identified by Rapid-Neo may provide predictive values for both targeted therapy and immunotherapy responses, supporting their integration into routine clinical decision-making.