Outcomes With Local Therapy and Tyrosine Kinase Inhibition in Patients With <i>ALK</i>/<i>ROS1</i>/<i>RET</i>-Rearranged Lung Cancers.

Abstract

Local therapy prolongs progression-free survival in patients with oligometastatic non-small-cell lung cancers treated with chemotherapy. We previously reported that local therapy also prolongs survival and time to next therapy in patients on tyrosine kinase inhibitors (TKIs) for <i>EGFR</i>-mutant lung adenocarcinomas. Here, we investigate the role of local therapy in patients progressing on TKIs for <i>ALK</i>/<i>ROS1</i>/<i>RET</i>-rearranged lung adenocarcinomas. Patients with advanced <i>ALK</i>/<i>ROS</i>/<i>RET</i>-rearranged lung adenocarcinomas who underwent radiation, surgery, or percutaneous thermal ablation from 2012 to 2020 for progression on an ALK/ROS1/RET TKI were included. Progression patterns were identified. Times from local therapy to progression, next therapy, and death were measured. Sixty-one patients with <i>ALK</i> (n = 37), <i>ROS1</i> (n = 12), and <i>RET</i> (n = 12) fusions were identified. Patients received radiotherapy (92%), surgery (13%), and percutaneous thermal ablation (8%). Local therapy was administered for solitary/oligoprogressive (94%) or polyprogressive (6%) disease. For most patients (85%), local therapy addressed all progressing sites. The median times from any local therapy to subsequent progression and next systemic therapy were 6.8 months (95% CI, 5.1 to 8.1) and 10 months (95% CI, 8.4 to 15.3), respectively. Third or greater local therapy was associated with shorter time to progression and next therapy than first/second local therapies (hazard ratio, 4.97; <i>P</i> < .001 and hazard ratio, 2.48; <i>P</i> < .001). The median overall survival from first local therapy was 34 months (95% CI, 26 to not reached). Local therapy for progression on ALK, ROS1, or RET TKIs is associated with clinically meaningful time on continued TKI therapy beyond progression, especially earlier in the course of disease.