Pivotal ARROS-1 Efficacy and Safety Data: Zidesamtinib in TKI Pre-treated Patients with Advanced/Metastatic ROS1+NSCLC
Recommended Citation
Drilon AE, Chul Cho B, Lin JJ, Solomon BJ, Lin C, Johannes de Langen A, Felip E, Neal JW, Liu SV, Soo RA, Kao S, Wolf J, Liu G, Baik CS, Dooms C, Nagasaka M, van der Wekken AJ, Camidge D, Yoshida T, Lin C, Chang G, Ahn M, Bauman JR, Gadgeel SM, Calles A, Pons-Tostivint E, Shao Weng Tan D, Johnson M, Bennati C, Spitaleri G. Pivotal ARROS-1 Efficacy and Safety Data: Zidesamtinib in TKI Pre-treated Patients with Advanced/Metastatic ROS1+NSCLC. J Thorac Oncol 2025; 20(10):1.
Document Type
Conference Proceeding
Publication Date
10-1-2025
Publication Title
J Thorac Oncol
Keywords
ROS1, TKI, zidesamtinib, Oncology, Respiratory System
Abstract
Introduction: In ret proto-oncogene (RET)–rearranged lung cancers, data on the frequency of brain metastases and, in particular, the outcomes of multikinase inhibitor therapy in patients with intracranial disease are not well characterized. Methods: A global, multi-institutional registry (cohort A, n = 114) and a bi-institutional data set (cohort B, n = 71) of RET-rearranged lung cancer patients were analyzed. Patients were eligible if they had stage IV lung cancers harboring a RET rearrangement by local testing. The incidence of brain metastases and outcomes with multikinase inhibitor therapy were determined. Results: The frequency of brain metastases at the time of diagnosis of stage IV disease was 25% (95% confidence interval [CI]: 18%–32%) in all patients from both cohorts. The lifetime prevalence of brain metastasis in stage IV disease was 46% (95% CI: 34%–58%) in patients for whom longitudinal data was available. The cumulative incidence of brain metastases was significantly different (p = 0.0039) between RET-, ROS1-, and ALK receptor tyrosine kinase (ALK)–rearranged lung cancers, with RET intermediate between the other two groups. Although intracranial response data was not available in cohort A, the median progression-free survival of multikinase inhibitor therapy (cabozantinib, vandetanib, or sunitinib) in patients with brain metastases was 2.1 months (95% CI: 1.3–2.9 months, n = 10). In cohort B, an intracranial response was observed in 2 of 11 patients (18%) treated with cabozantinib, vandetanib (± everolimus), ponatinib, or alectinib; the median overall progression-free survival (intracranial and extracranial) was 3.9 months (95% CI: 2.0–4.9 months). Conclusions: Brain metastases occur frequently in RET-rearranged lung cancers, and outcomes with multikinase inhibitor therapy in general are suboptimal. Novel RET-directed targeted therapy strategies are needed.
Volume
20
Issue
10
First Page
1
