Osimertinib and stereotactic radiosurgery for brain metastases in EGFR mutated lung cancer - The STARLET joint analysis of OUTRUN and LUOSICNS randomised trials
- Author(s)
- Lee, CK; Lefresne, S; Soon, YY; Robledo, K; Nichol, A; Sahgal, A; Pinkham, MB; Melosky, B; Huang, Y; McDermott, R; Tham, IWK; Parmar, A; Tey, JCS; Liu, M; Solomon, BJ; Sacher, A; Leong, CN; Laskin, J; Koh, WY; Menjak, IB; Ang, Y; Shultz, DB; Low, J; Doherty, M; Yong, C; Lim, MC; Tan, AP; Soo, RA; Hegi-Johnson, F; Ho, C;
- Journal Title
- Journal of Thoracic Oncology
- Publication Type
- Online publication before print
- Abstract
- INTRODUCTION: Clinical guidelines recommend upfront osimertinib monotherapy for asymptomatic brain metastases (BM) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), despite a lack of randomised trial evidence. We conducted two randomised phase II trials, OUTRUN and LUOSICNS, to evaluate the efficacy and safety of upfront stereotactic radiosurgery (SRS) plus osimertinib versus osimertinib in this patient population. METHODS: Participants with up to ten BM amenable to SRS were randomised 1:1 to SRS followed by osimertinib (80mg daily) or osimertinib monotherapy. SRS was delivered as a single or multi-fraction regimen. The primary endpoint was 12-month intracranial progression-free survival (ic-PFS). Key secondary endpoints include overall survival (OS), patterns of intracranial progression, and safety. Data from both trials were prospectively pooled for a joint analysis. RESULTS: Overall, 79 participants were randomised. At a median follow-up of 39.0 months, 12-month ic-PFS was not significantly different between SRS plus osimertinib (n = 39) over osimertinib monotherapy (n = 40) (11%, 95% CI, -10% to 32%, P=.31; median ic-PFS 21.9 versus 17.2 months). Median OS was 46.1 versus 29.1 months. Among those with intracranial progression, 35% in the SRS plus osimertinib group and 57% in the osimertinib monotherapy group underwent SRS at progression. Grade 3/4 radionecrosis occurred in 5% of participants treated with SRS plus osimertinib. CONCLUSIONS: Adding upfront SRS to osimertinib did not significantly improve 12-month ic-PFS in EGFR mutant NSCLC with BM. This represents the first randomised evidence supporting the use of osimertinib monotherapy as upfront therapy in minimally symptomatic patients with low burden BM.
- Department(s)
- Medical Oncology; Radiation Oncology
- Publisher's Version
- https://doi.org/10.1016/j.jtho.2026.01.001
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- Refer to copyright notice on published article.
Creation Date: 2026-01-22 02:13:26
Last Modified: 2026-01-22 02:13:47