OBJECTIVES: Emerging targeted therapies have broadened treatment options for patients with advanced non–small cell lung cancer (advNSCLC), including those with rearrangements of ROS1 (ROS1+) and NTRK (NTRK+). However, limited availability of biomarker testing data hinders disease burden and economics analyses in these patients. This study aims to estimate the prevalence, incidence, and characteristics of ROS1+ and NTRK+ patients who underwent comprehensive genomic profiling in real-world settings.

METHODS: This study included patients with advNSCLC (stage IIIB-IVB at initial diagnosis or early stage with subsequent recurrence or progression) from the nationwide deidentified Flatiron Health-Foundation Medicine NSCLC clinicogenomic database; data originated from approximately 280 US cancer clinics with a cutoff of June 30, 2023. Baseline characteristics and treatments were summarized by ROS1 and NTRK status.

RESULTS: Among 18,261 eligible patients, 17,395 (95%) were tested and had a valid result for ROS1 and 16,877 (92%) for NTRK. Prevalence was 1.02% for ROS1+ and 0.18% for NTRK+. Median time from diagnosis of advanced disease to first test result was 35 (22-86) days for ROS1 and 43 (26-189) days for NTRK. From 2014 to 2022, incidence of ROS1+ varied from 515 to 1413 per 100,000 advNSCLC cases each calendar year and 38 to 316 for NTRK+. Compared with patients without driver mutations, ROS1+ patients were more likely to be female, nonsmokers, and younger and have nonsquamous cell carcinoma histology and metastatic disease at diagnosis. NTRK+ patients were more likely to be female and nonsmokers and have squamous cell carcinoma histology. The most common first-line treatments were targeted therapy (50%) for ROS1+ patients and chemotherapy (39%) and immunotherapy (35%) for NTRK+ patients.

CONCLUSIONS: This study presents the most recent epidemiology data on a large US-based real-world cohort of patients with ROS1+ and NTRK+ advNSCLC. It provides insights into characteristics and treatment approaches in these patient subgroups.