Researchers of the phase 2 NorthStar trial (NCT03410043) showed that adding local consolidative therapy (LCT; surgery and/or radiation) to osimertinib significantly prolonged progression-free survival (PFS) in metastatic EGFR-mutant non-small cell lung cancer (NSCLC). After 6 to 12 weeks of induction osimertinib, 120 patients without progression were randomized to continue osimertinib alone or with LCT. Median PFS improved from 17.5 months with osimertinib to 25.3 months with osimertinib plus LCT (HR, 0.66; 95% CI, 0.50–0.87; 1-sided P=.025). Benefit was consistent across key subgroups: exon 19 deletion (39.8 vs 22.4 months; HR, 0.57) and L858R (19.0 vs 11.0 months; HR, 0.60), and in both oligometastatic (≤3 lesions) and polymetastatic (>3 lesions) disease. Among patients with polymetastatic disease achieving complete LCT, median PFS reached 27.9 months versus 14.5 months with partial LCT.
Safety was acceptable, with no excess toxicity from the addition of LCT. Common treatment-related adverse events on the combination were mainly grade 1 to 2. LCT-specific events such as pneumonitis were infrequent and largely low grade. No grade 4/5 LCT-related events occurred. These results address a major unmet need by delaying resistance and systemic progression, supporting osimertinib plus LCT as a safe, effective strategy to extend disease control in advanced EGFR-mutant NSCLC.
Reference: Rosa K. Osimertinib Plus Local Consolidative Therapy Significantly Extends PFS in EGFR-Mutant NSCLC. OncLive. Published October 17, 2025. Accessed October 27, 2025. https://www.onclive.com/view/osimertinib-plus-local-consolidative-therapy-significantly-extends-pfs-in-egfr-mutant-nsclc
