Osimertinib in combination with local consolidative therapy of radiation and/or surgery led to a significant extension of progression-free survival for patients with EGFR-mutant metastatic non–small cell lung cancer (NSCLC), according to findings from the phase II NorthStar trial presented at the European Society for Medical Oncology (ESMO) Congress 2025 (Abstract LBA72).
“For patients with EGFR-mutant NSCLC, adding the targeted therapy osimertinib alongside these other treatments not only helped prevent progression of the primary tumor, but also metastatic sites,” said principal investigator Yasir Elamin, MD, Associate Professor of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center. “This is an encouraging step forward and suggests osimertinib could become a valuable therapeutic addition for these patients.”
The study authors suggested that the results could support the integration of local consolidative therapy into the treatment paradigm for patients receiving EGFR-targeted therapy in appropriately selected patients, and could inform future standards of care for this patient population.
Study Methods
The randomized phase II NorthStar trial assessed the benefits of adding local consolidative therapy to standard-of-care osimertinib for patients with EGFR-mutant metastatic NSCLC. A total of 119 patients, who were naive to tyrosine kinase inhibition or had acquired an EGFR T790M mutation without receiving a prior third-generation EGFR tyrosine kinase inhibitor, received osimertinib monotherapy for 6 to 12 weeks. If they did not have disease progression, they were then randomly assigned to receive either continued osimertinib monotherapy or the addition of local consolidative therapy.
Key Study Findings
In the investigational arm (n = 56), consolidation therapy consisted of radiation in 59% of patients, surgery in 29%, and both in 12%.
The median progression-free survival in the osimertinib plus local consolidative therapy arm was 25.4 months compared with 17.0 months in the osimertinib monotherapy arm (hazard ratio [HR] = 0.60; 95% confidence interval [CI] = 0.40–0.92; P = .02).
Ninety-six percent of patients in each arm experienced an adverse event of any grade. Grade 3 or higher adverse events were reported in 16% of patients receiving osimertinib monotherapy and in 29% of patients receiving osimertinib plus consolidative therapy. The most common events were skin disorders, anorexia, and dyspnea, which was significantly more common in the investigational combination arm. No adverse events observed were unexpected.
Disclosure: The trial was funded by the National Comprehensive Cancer Network and AstraZeneca. For full disclosures of the study authors, visit ctimeetingtech.com/esmo2025.
