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

Abstract

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.

FIG 1.

Flowchart illustrating subject inclusion on the basis of the study criteria. MSK, Memorial Sloan Kettering; TKI, tyrosine kinase inhibitor.

FIG 2.

(A) Time to first progression and (B) time to next systemic therapy start from the start of the first included local therapy for all 61 patients.

FIG 3.

Swimmer plot depicting patient courses following first included local therapy for all 61 included patients: (A) Patients are sorted by oncogenic fusion. (B) Patients are grouped on the basis of the presence of CNS involvement. TKI, tyrosine kinase inhibitor.

FIG 4.

Patterns of failure (A) before and (B) after local therapy, with the number of progressing sites before local therapy and at first progression after local therapy in all 93 included local therapies.