Timeliness of Newer Targeted Therapy and Survival in Lung Cancer: A Population-Based Analysis

PURPOSE Newer targeted therapy (NTT), addressing alterations in BRAF , MET , NTRK , ROS1 , and RET has become a common therapeutic option for non–small cell lung cancer (NSCLC). To date, only RET inhibitor has been shown in a phase III study to confer a survival advantage when used in the frontline setting. This study investigates timing of NTT and its impact on survival using a large, population-base data set. METHODS We searched a nationwide, electronic health record–derived, deidentified database for patients with advanced NSCLC treated with NTT between May 2014 and March 2023. Time to treatment initiation (TTI) was calculated from the diagnosis of advanced NSCLC. Landmark analytic technique was used to address immortal time bias. RESULTS Among 857 patients analyzed, the median TTI was 3.8 months. By month 2 or month 3 after diagnosis, patients who already initiated NTT had significantly better survival than those who had not initiated NTT at those time points: Hazard ratio (HR), 0.65 (95% CI, 0.53 to 0.81; P < .001) and HR, 0.69 (95% CI, 0.55 to 0.85; P = .001), respectively. A multivariate analysis indicated that delayed TTI was an independent prognostic factor of decreased survival, along with impaired performance status and squamous cell carcinoma histology. Subgroup analyses excluding RET inhibitor still demonstrated a statistically significant survival advantage in favor of earlier NTT initiation. CONCLUSION Among advanced NSCLC patients undergoing NTT, survival was significantly better among those who began treatment within 2 or 3 months after diagnosis than those whose treatment was delayed.