Standard targeted therapy implementation for driver alterations newly identified by comprehensive genomic profiling...

Comprehensive genomic profiling (CGP) can identify oncogenic drivers missed by routine molecular testing in advanced or recurrent non-small cell lung cancer (NSCLC). However, the availability of standard targeted therapy, treatment implementation, and survival relevance of these CGP-identified new drivers remain unclear.

Using the nationwide Center for Cancer Genomics and Advanced Therapeutics database, we analyzed patients with advanced or recurrent NSCLC without clinically known driver alterations before CGP. CGP-identified new drivers were classified as actionable or non-actionable according to standard targeted therapy availability in Japan. We evaluated prevalence, treatment implementation, and overall survival (OS) from CGP registration.

Among 2,296 patients, 855 had CGP-identified new drivers, of whom 495 (57.9%) had actionable alterations. Matched targeted therapy was administered to 191 patients with actionable alterations (38.6%) and to 84.5% of those with documented post-CGP systemic therapy. Median OS was longest in patients with actionable CGP-identified new drivers, followed by driver-negative patients and those with non-actionable CGP-identified new drivers (18.9, 11.4, and 10.2 months, respectively; log-rank P < 0.001). In multivariable analysis, actionable CGP-identified new drivers were associated with longer OS than driver-negative status (adjusted hazard ratio, 0.71; 95% confidence interval, 0.59-0.84; P < 0.001), whereas non-actionable new drivers were not. Sensitivity analyses using time-specific drug-availability definitions yielded consistent findings.

CGP identified new drivers with available standard targeted therapy in patients with advanced or recurrent NSCLC. The clinical relevance of CGP-identified new driver detection appears linked to standard targeted therapy availability and translation of actionable findings into matched therapy.