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Updated: Jun 30, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Real-world treatment sequencing and survival in ROS1-Rearranged NSCLC across evolving treatment eras: Findings from
Malinda Itchins1, Marliese Alexander2, Steven Kao3
1Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
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.
Insights
Real-world data show later-generation ROS1 inhibitors significantly improve progression-free survival in ROS1-rearranged non-small cell lung cancer (NSCLC). Favorable outcomes are linked to early molecular testing and clinical trial participation.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) with ROS1 rearrangements is rare.
- Real-world data on treatment sequencing and survival for ROS1-positive NSCLC are limited.
- Targeted therapies have improved outcomes, but understanding treatment patterns is crucial.
Purpose of the Study:
- To analyze real-world treatment sequencing and survival outcomes in ROS1-rearranged NSCLC.
- To evaluate the impact of different generations of ROS1 inhibitors on patient survival.
- To identify factors associated with improved outcomes in this rare cancer subtype.
Main Methods:
- Analysis of the Australian multicentre AURORA cohort (2012-2025) including 115 ROS1-positive NSCLC cases.
- Extraction of demographic, diagnostic, and treatment data, mapping systemic therapy sequences.
- Estimation of progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox models.
Main Results:
- 115 ROS1-positive NSCLC cases identified (2.2% of cohort); 90% treated for advanced disease.
- First-line later-generation ROS1 inhibitors showed improved median OS (80 months) compared to early-generation (56 months).
- Median PFS was 17 months with early-generation vs. 48 months with later-generation first-line ROS1 inhibitors.
Conclusions:
- Real-world data demonstrate evolving treatment strategies for ROS1-rearranged NSCLC.
- Access to ROS1 inhibitors, particularly later-generation agents, and clinical trial enrollment contribute to favorable survival.
- Reflex molecular testing is key for timely diagnosis and effective treatment initiation.
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