Purpose: 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 EGFR-mutant lung adenocarcinomas. Here, we investigate the role of local therapy in patients progressing on TKIs for ALK/ROS1/RET-rearranged lung adenocarcinomas.
Materials and methods: Patients with advanced ALK/ROS/RET-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.
Results: Sixty-one patients with ALK (n = 37), ROS1 (n = 12), and RET (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; P < .001 and hazard ratio, 2.48; P < .001). The median overall survival from first local therapy was 34 months (95% CI, 26 to not reached).
Conclusion: 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.