Extending the Duration of Efficacy of Targeted Therapies with Radiation to Oligoprogressive Disease (OPD) in Oncogene-Driven Metastatic Non-Small Cell Lung Cancer (NSCLC)

Abstract

We evaluated the role of local ablative radiotherapy (LAR) to sites of OPD in extending the duration of efficacy of the targeted therapies for patients with oncogene-driven metastatic NSCLC. From January 2015 to February 2019 we identified 81 patients with metastatic NSCLC EGFR, ALK, ROS1, and BRAF (n = 50, 20, 7, and 4, respectively) driver mutations on targeted therapies with OPD of ≤ 5 sites per LAR course treated at our center. Progression free survival-1 (PSF1) on targeted therapy was defined as time from targeted agent use to the LAR course for OPD. PFS2 was defined as start of LAR to change of systemic therapy. If more than 1 LAR course was administered on the same targeted therapy, PFS2 included the total time interval until change of system therapy. CNS and regional lymph node regions were each considered a single site of disease. Overall survival and PFS were estimated using the Kaplan-Meier method and analyzed using the log-rank test. Median PFS1 on targeted therapy was 8.7 months for all patients. Median PFS2 after LAR course(s) was an additional 7.6 months. The median PFS2 for CNS only OPD was 8.0 months whereas the median PFS2 for extracranial only OPD was 6.8 months (log-rank p=0.236). The resulting median overall time on the same targeted therapy was 17.3 months in patients who received LAR for OPD which was statically significant compared to PSF1 of 8.7 months (log-rank p<0.0001). Overall, there were 133 courses of LAR among the 81 patients, with mean, median, and range of 1.6, 1, and 1-5 courses per patient, respectively. The number of sites treated per LAR course had a mean, median, and range of 1.4, 1, and 1-5 sites per course, respectively. Median overall survival in the cohort was 62.0 months. In patients with oncogene-driven NSCLC, one or more courses of LAR to sites of OPD significantly increased the duration of efficacy of targeted therapies by 7.6 months and nearly doubled the time on a given targeted agent. LAR to OPD in oncogene-driven NSCLC represents a highly effective strategy to maximize the duration of access to targeted therapies.