Key Clinical Summary: 

• Design/Population: The phase 3 NorthStar trial randomized patients with metastatic EGFR-mutated non-small cell lung cancer without progression after induction osimertinib to receive osimertinib alone or in combination with local consolidative therapy. This secondary analysis evaluated radiotherapy approaches, patterns of failure, and predictors of benefit.
• Key Outcomes: Addition of local consolidative therapy to osimertinib significantly improved progression-free survival, particularly among patients without residual thoracic nodal disease or pleural effusion after induction therapy. Patients with persistent disease did not derive benefit, and most recurrences after local consolidative therapy were distant and occurred outside treated fields.
• Clinical Relevance: These findings support the use of local consolidative therapy in carefully selected patients with favorable response to induction osimertinib. Residual nodal disease and pleural effusion may help guide patient selection, as benefit appears limited in these subgroups.

Results from the phase 2 NorthStar trial demonstrate that adding local consolidative therapy to osimertinib significantly improves outcomes among patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). 

These results were presented at the European Lung Cancer Congress in Copenhagen, Denmark, by Samuel Ghandi, MD, PhD, MD Anderson Cancer Center, Houston, Texas. 

In this study, 119 patients without disease progression after 6 to 12 weeks of osimertinib were randomized to receive osimertinib alone (n = 63) or in combination with either radiotherapy (n = 33), surgery (n = 17), or both radiotherapy and surgery (n = 6). Researchers evaluated patterns of failure and clinical predictors of progression-free survival (PFS).

At analysis, among patients without residual thoracic nodal disease after induction osimertinib, median PFS was 41.5 months in the combination arm and 19.6 months in the osimertinib arm (hazard ratio [HR], 0.43; 90% confidence interval [CI], 0.23 to 0.78; P = .008). In contrast, among patients with persistent thoracic nodal disease, median PFS was 19 months in the combination arm and 17.5 months in the osimertinib arm (HR, 0.94; 90% CI, 0.61 to 1.46; P = .41).

Similarly, among patients without persistent pleural effusion, median PFS was 32.7 months in the combination arm and 22.3 months in the osimertinib arm (HR, 0.63; 90% CI, 0.39 to 1.02; P = .057). In patients with persistent pleural effusion, median PFS was 15.3 months in the combination arm and 12.9 months in the osimertinib arm (HR, 0.90; 90% CI, 0.52 to 1.55; P = .37).

Disease recurrence occurred in 37 patients who underwent local consolidative therapy, 62% of which occurred at new metastatic sites. Among the 24 patients who received radiotherapy, 8% of recurrences were in-field and 92% occurred outside the treatment field.

“Clearance of thoracic nodal disease and pleural effusion following induction [osimertinib] emerged as potential predictors of benefit from [local consolidative therapy],” concluded Dr Gandhi et al. “Failures after [local consolidative therapy] were predominantly distant, occurring outside the [radiotherapy] field and most commonly at new metastatic sites.” 

Source:

Gandhi S. Predictors of benefit from local consolidative therapy and patterns of failure for metastatic EGFR-mutant NSCLC: A secondary analysis of NorthStar, a phase II randomized clinical trial. Presented at European Lung Cancer Congress. March 28 - 28, 2026. Copenhagen, Denmark. LBA3.