Synapse - Outcomes with local therapy and tyrosine kinase inhibition in patients with ALK/ROS1/RET-rearranged lung cancers

Outcomes with local therapy and tyrosine kinase inhibition in patients with ALK/ROS1/RET-rearranged lung cancers Journal Article

Authors:	Hubbeling, H.; Choudhury, N.; Flynn, J.; Zhang, Z. G.; Falcon, C.; Rusch, V. W.; Park, B. J.; Ziv, E.; Shaverdian, N.; Gelblum, D. Y.; Shepherd, A. F.; Simone, C. B. 2nd; Wu, A. J.; Gomez, D. R.; Drilon, A.; Rimner, A.
Article Title:	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. (c) 2022 by American Society of Clinical Oncology
Keywords:	radiotherapy; progression; resistance; impact; benefit; crizotinib; ablative therapy; oligoprogressive disease
Journal Title:	JCO Precision Oncology
Volume:	6
ISSN:	2473-4284
Publisher:	American Society of Clinical Oncology
Date Published:	2022-10-06
Start Page:	e2200024
Language:	English
ACCESSION:	WOS:000975488400035
DOI:	10.1200/po.22.00024
PROVIDER:	wos
PMCID:	PMC9848570
PUBMED:	36201714
Notes:	Article -- -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Andreas Rimner -- Source: Wos