Top Line: Osimertinib is a 3rd-generation EGFR TKI that has good intracranial activity in patients with metastatic, EGFR mutated NSCLC.
The Study: Because of this, some consider deferring radiation for patients with small, asymptomatic brain metastases. However, there is a lack of randomized data on this topic. OUTRUN and LUOSICNS were two randomized trials that compared osimertinib with or without SRS for patients with EGFR mutated NSCLC brain metastases. This combined analysis included 79 patients with up to 10 brain metastases amenable to SRS. In OUTRUN, the prescription was 18-20 Gy in 1 fraction or 24 Gy in 3 fractions. In LUOSICNS, the prescriptions were 15-20 Gy in 1 fraction, 21-27 Gy in 3 fractions, or 25-40 Gy in 5 fractions. Osimertinib started immediately after SRS in both trials. The median brain metastasis diameter was 1.1cm, and most patients had multiple lesions. Both trials were designed to detect a 15% improvement in intracranial PFS with SRS. At 12 months, the rate of icPFS was 68% with osimertinib plus SRS versus 57% with osimertinib alone, which did not reach statistical significance. Median icPFS was 21.9 months with SRS versus 17.2 without. The cumulative rate of intracranial progression at 12 months was 16% with SRS and 13% without. Notably, the benefit of SRS increased with lesion size. The optimal cutpoint for benefit from SRS was a sum of all lesion diameters of 1.9 cm.
TBL: In this combined analysis of two small randomized trials, adding SRS to osimertinib for limited EGFR mutated NSCLC brain metastases did not dramatically improve intracranial PFS. | Lee, J Thorac Oncol 2026
The Study: Because of this, some consider deferring radiation for patients with small, asymptomatic brain metastases. However, there is a lack of randomized data on this topic. OUTRUN and LUOSICNS were two randomized trials that compared osimertinib with or without SRS for patients with EGFR mutated NSCLC brain metastases. This combined analysis included 79 patients with up to 10 brain metastases amenable to SRS. In OUTRUN, the prescription was 18-20 Gy in 1 fraction or 24 Gy in 3 fractions. In LUOSICNS, the prescriptions were 15-20 Gy in 1 fraction, 21-27 Gy in 3 fractions, or 25-40 Gy in 5 fractions. Osimertinib started immediately after SRS in both trials. The median brain metastasis diameter was 1.1cm, and most patients had multiple lesions. Both trials were designed to detect a 15% improvement in intracranial PFS with SRS. At 12 months, the rate of icPFS was 68% with osimertinib plus SRS versus 57% with osimertinib alone, which did not reach statistical significance. Median icPFS was 21.9 months with SRS versus 17.2 without. The cumulative rate of intracranial progression at 12 months was 16% with SRS and 13% without. Notably, the benefit of SRS increased with lesion size. The optimal cutpoint for benefit from SRS was a sum of all lesion diameters of 1.9 cm.
TBL: In this combined analysis of two small randomized trials, adding SRS to osimertinib for limited EGFR mutated NSCLC brain metastases did not dramatically improve intracranial PFS. | Lee, J Thorac Oncol 2026