Mapping Real-world Rebiopsy Events to Treatment Trajectories in EGFR/ALK/ROS1-Driven Non-small-cell Lung Cancer: Insights from the AURORA Cohort.

[BACKGROUND] Rebiopsy to identify resistance mechanisms and guide individualised treatment plans for systemic therapy is emerging as a fundamental practice in the management of oncogene-driven non-small cell lung cancer (NSCLC). The application of rebiopsy in real-world practice remains incompletely characterised.

[PATIENTS AND METHODS] This retrospective cohort study included patients with EGFR-, ALK-, and ROS1-positive NSCLC from the Australasian AURORA cohort treated at an Australian academic cancer centre (ACTRN12625000038493). Eligible adults were enrolled 2012-2025 with oncogenic driver status confirmed by fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS). Data collected included biopsy timing, indication, and context, alongside systemic therapy, surgery, and radiotherapy. Progression re-biopsies were further characterised by molecular testing modalities, identification of acquired resistance mechanisms and evidence of histological transformation. Treatment trajectories were visualised using Swimmer plots to map biopsy and rebiopsy events across longitudinal lines of therapy, stratified by oncogenic driver.

[RESULTS] This analysis included 621 biopsies from 281 patients: 105 EGFR, 141 ALK, and 35 ROS1. All patients had a diagnostic biopsy (20% more than one); additional biopsies occurred at resection (20%), during treatment (11%), and during surveillance (2%). Among patients with disease progression, 56% underwent rebiopsy overall, with rates increasing over time from 51% before 2018 to 57% during 2018-2021 and 70% during 2022-2025 (P = 0.04).

[CONCLUSION] This real-world analysis provides contemporary insight into rebiopsy practices and longitudinal treatment patterns in oncogene-driven NSCLC. By mapping biopsy events to treatment trajectories, this study highlights evolving real-world practice, with rebiopsy rates at progression increasing over time across EGFR, ALK, and ROS1 cohorts.