The NorthStar phase II randomized study evaluated osimertinib (OSI) with or without local consolidative therapy (LCT) for metastatic EGFR-mutant non-small cell lung cancer (NSCLC) presented at ESMO 2025 by Yasir Y. Elamin, MD during the Proffered Paper session NSCLC metastatic.
Background
Osimertinib is the standard of care for EGFR-mutant metastatic NSCLC, but most patients ultimately progress. The phase II NorthStar trial tested whether adding local consolidative therapy (LCT) to ongoing osimertinib can extend disease control.
Methods
Adults with EGFR-mutant metastatic NSCLC who were either TKI-naïve or had acquired T790M (without prior third-generation EGFR TKI) received osimertinib 80 mg daily for 6–12 weeks. Patients without progression were randomized 1:1 to continue osimertinib alone or osimertinib + LCT (radiation and/or surgery). Stratification included therapy line, metastatic burden (≤3 vs >3 lesions), induction response (PR vs SD), and CNS involvement. Primary endpoint: progression-free survival (PFS).
Results
Population & treatment: Of 119 randomized (63 osimertinib alone; 56 osimertinib+LCT), most had polymetastatic disease (>3 lesions: 59% vs 57%). LCT comprised radiation (59%), surgery (29%), or combined (12%).
Efficacy (primary endpoint met):
- Median PFS: 25.4 months with osimertinib+LCT vs 17.0 months with osimertinib alone.
- HR 0.60 (95% CI 0.40–0.92; p=0.02) → ~40% lower risk of progression.
Safety
Any-grade AEs occurred in >96% of patients in both arms; grade ≥3 AEs were ~16% with osimertinib alone vs 29% with osimertinib+LCT. Common toxicities were skin disorders (65.1% vs 64.4%), anorexia (19.0% vs 16.9%), and dyspnea (17.5% vs 30.5%). No unexpected safety signals were observed, supporting feasibility of integrating LCT with ongoing osimertinib.
Conclusions
In patients with EGFR-mutant metastatic NSCLC who achieve early disease control on osimertinib, adding LCT significantly prolongs PFS, including in those with polymetastatic burden. These data support multidisciplinary evaluation for LCT during first-line EGFR-targeted therapy and may inform future standards of care.
You can read the full abstract here.