Breaking barriers: Real-world data on immunotherapy in non-small cell lung cancer with large brain metastases.

e14002 Background: Non-small cell lung cancer (NSCLC) patients with large brain metastases (BrM) defined as > 2 cm historically face grim prognoses. Immunotherapy, emerging as a state-of-the-art treatment in NSCLC treatment, has not been extensively studied in the context of large BrM. The use of immunotherapy in these patients is complicated by factors such as steroids use and local interventions like surgery and/or radiation treatment. Methods: We conducted a retrospective study across three MedStar Georgetown Cancer Network sites to evaluate outcomes in NSCLC patients with large BrM. Inclusion criteria comprised of patients aged 18 years or older with NSCLC diagnosed between 01/01/17 to 12/31/2022 who started immunotherapy after the diagnosis of at least one BrM 2 cm or more in diameter. Intracranial progression free survival (PFS), overall survival (OS), and relevant clinical factors were analyzed. Steroid use was not included due to documentation limitations. Cox penalized regression was used to assess PFS and OS while power analysis was not done due to the sample size. Results: The study included 36 patients all of whom underwent neurosurgery and/or radiation before starting immunotherapy. Median follow up duration was 17.6 months. The population was 58.3% female, median age 64.4 years, 77.8% lung adenocarcinoma, 91.7% received pembrolizumab for immunotherapy, and median duration of immunotherapy was 178 days. Median intracranial PFS was 9.2 months and median OS reached 31 months. The hazard ratio (HR) was 0.07 (95% confidence interval (CI) 0.02-0.26) for intracranial PFS in patients who received at least 90 days of immunotherapy compared to those who received less than 90 days of immunotherapy. Each additional 30 days of immunotherapy was associated with an OS HR 0.77 (95% CI 0.67-0.90). Higher PD-L1 status was not associated with improved outcomes. Conclusions: The study highlights the potential of immunotherapy as a valuable treatment for NSCLC patients with large BrM, a population often excluded from clinical trials. In our retrospective analysis, extended immunotherapy demonstrated positive impacts on both intracranial PFS and OS. Future directions should focus on prospective evaluation of the optimal timing of immunotherapy relative to upfront large BrM treatment, with a specific emphasis on understanding the role of steroids dosing in this context.