Real-world data analysis of genomic profiling-matched targeted therapy outcomes in patients with fusion-positive NSCLC

Authors Jyoti Patel, MD, Rotem Ben-Shachar, Kaveri Nadhamuni, Mark Carty, Rafi Pelossof, Ira Klein, Halla Nimeiri, Aggarwal, Charu, Gentzler, Ryan


While clinical oncology societies such as ESMO have recommended the use of Comprehensive Genomic Profiling (CGP) to identify patients eligible for targeted treatment, full utilization of the potential benefits of CGP has not yet occurred in routine clinical practice. Here we assess the compliance to ESMO targeted therapy recommendations and associated outcomes for CGP-based ALK, RET, ROS1, and NTRK fusions detected in a large real-world, observational dataset of advanced NSCLC patients.


We retrospectively analyzed de-identified stage IV or metastatic NSCLC records from the Tempus database which encompasses molecular and clinical data from hundreds of clinics across the United States sequenced with the Tempus xT assay (DNA and whole-exome capture RNA NGS) from 2018-2022. Therapeutic adoption was analyzed in cases with ≥30 days of medication data post-sequencing. Real-world overall survival (rwOS) was defined as the interval from start of medication prescribed after sequencing to date of death, censored on the last known physician encounter. A cox proportional hazards model was fit to evaluate the relationship between matched targeted therapy compliance and rwOS in fusion-positive patients.


Among 1,950 patients that met study inclusion criteria, N= 65 (3.3%) had a fusion detected by CGP (N=38 ALK fusions, N=15 RET fusions, N=11 ROS1 fusions and N= 1 NTRK fusion). The overall compliance rate of targeted therapy was 82% (N=53). The median time from sequencing to start of targeted therapy was < 1 month. Fusion-positive patients receiving matched therapy had significantly longer rwOS than those that did not receive matched therapy (HR=0.13, p<0.001). ALK-positive patients receiving matched therapy had significantly longer rwOS than those that did not receive matched therapy, (HR=0.12, p<0.05).


This study demonstrates that in a real-world, retrospective cohort, most oncologists utilized CGP to timely treat patients with ESMO-recommended targeted therapy for fusion-positive advanced NSCLC. More importantly, CGP-matched guideline-recommended treatment is associated with improved rwOS. Future studies are needed to understand the gap in compliance with matched targeted therapy.