Real-world treatment sequencing and survival in ROS1-rearranged NSCLC across evolving treatment eras: Findings from the AURORA multi-centre registry (AURORA-ROS1)
Author Identifier (ORCID)
Abstract
Background: Targeted therapies have improved outcomes in ROS1-rearranged NSCLC “ROS1”, but real-world evidence on evolving treatment sequencing and survival to understanding this rare cancer remains sparse.
Methods: ROS1 cases identified from the Australian multicentre AURORA cohort between 2012 and 2025 were analysed. Demographic, diagnostic, and treatment data were extracted, with systemic therapies mapped to report sequencing and discontinuation. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods. Multivariable Cox models assessed clinical correlates of outcome.
Results: Among 5,189 NSCLC cases within AURORA, 115 (2.2 %) were ROS1 positive. Median age was 58 years; 64 % female; 85 % had de novo advanced disease, 14 % baseline brain metastases. Amongst n = 16 with early-stage, 59 % recurred. In total n = 104/115 (90 %) were treated for advanced disease, median 2 lines; range 1–8, 32 % did not receive a second line. First-line ROS1-inhibitor therapy (ROS1i) was given to 74 % (n = 77), including early-generation (n = 63; crizotinib/entrectinib) and later-generation ROS1i's (n = 14; repotrectinib/zidesamtinib/lorlatinib). Across all lines, 96 % received a ROS1i including 63 % with later-generation, and 53 % participated in a clinical trial. Median PFS with first line early-generation ROS1i was 17 months(mo), 48mo for first line later-generation ROS1i (p = 0.071). Median OS was 56mo overall, 80mo with first line later-generation ROS1i. Median OS was 26mo in those with brain metastases at diagnosis versus 58mo without (p = 0.010) and 41mo in those with PD-L1 ≥ 50 % versus 62mo 0–49 % (p = 0.017).
Conclusion: This multicentre real-world cohort describes longitudinal ROS1 management with evolving treatments. Favourable survival likely reflects reflex molecular testing, access to ROS1i, and high clinical trial enrolment.
Keywords
AURORA, NSCLC, real-world, ROS1, survival, treatment
Document Type
Journal Article
Date of Publication
8-1-2026
Article Number
109500
E-ISSN
18728332
ISSN
01695002
Volume
218
PubMed ID
42365776
Publication Title
Lung Cancer
Publisher
Elsevier
School
Centre for Precision Health
RAS ID
100673
Funding Information
This study is supported by the Kha Kiang Khoo Memorial Award, Lung Foundation Australia. This research was performed in her memory, as a lady who was unfortunately not afforded time to trial ROS1 treatments for her disease.
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Recommended Citation
Itchins, M., Alexander, M., Kao, S., Nagrial, A., Brown, L. J., Bowyer, S., Parakh, S., Moore, M., Kong, B. Y., Yeo, N., Hughes, B. G., Arulananda, S., Chin, V., Warburton, L., Khoo, T., Mersiades, A. J., Leigh, L., Rogers, J., Pavlakis, N., & Solomon, B. J. (2026). Real-world treatment sequencing and survival in ROS1-rearranged NSCLC across evolving treatment eras: Findings from the AURORA multi-centre registry (AURORA-ROS1). Lung Cancer, 218, 109500. https://doi.org/10.1016/j.lungcan.2026.109500