2478 - PD-L1, Tumor Mutational Burden (TMB) and Intracranial Outcomes in Patients with Non-Small Cell Lung Cancer (NSCLC) and Brain Metastases

E. Adib^1,2, A. H. Nassar³, D. J. Kwiatkowski², and A. A. Aizer⁴; ¹Massachusetts General Hospital, Boston, MA, ²Brigham and Womens Hospital, Boston, MA, ³Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, CT, ⁴Department of Radiation Oncology, Dana-Farber Brigham Cancer Center, Boston, MA

Purpose/Objective(s): Brain metastases (BM) affect up to 50% of patients with NSCLC and are associated with poor prognosis in patients with non-targetable genomic alterations. Radiation forms the typical mainstay of intracranial management in such patients given the historically guarded intracranial efficacy of most systemic options. Immunotherapy-based approaches have shown promise but the extent that patients with BM may display extended survival with combination radiotherapeutic and immunotherapy-based approaches remains unclear. Materials/

Methods: We identified 160 patients harboring non-squamous NSCLC with 486 newly-diagnosed BM between 2015-2023 managed with brain-directed radiation (either stereotactic-based, SRT or whole brain radiation therapy, WBRT) and immune checkpoint inhibition within 3 months of radiation at Dana-Farber Cancer Institute/Brigham and Women’s Hospital (Boston, MA). PD-L1 tumor expression was categorized as <1%, 1-49%, 50-89%, and =90% based on immunohistochemistry. TMB was assessed via targeted next-generation sequencing. Cox-proportional hazards regression was used to assess all-cause mortality. Mixed-effects Fine-Gray models were used for per-metastasis outcomes, including rates of local control (LC) and radiation necrosis (RN).
Results: The median number of BM was 3 (IQR 1-7). Neurosurgical resection in advance of radiation was performed in 51/160 (32%) pts. SRT was used in 130/160 (81%) versus 30/160 (19%) patients treated with WBRT, respectively. Median follow-up time was 30.1 months (mo). Higher PD-L1 expression was associated with significantly longer overall survival (OS) with a median survival in patients with PD-L1<1%, 1-49%, 50-89% and =90% being 11.8, 14.4, 29.5 and 33.1 mo, respectively (Table). Two-year LC rates were excellent and similar across PD-L1 categories. Two-year rates of RN were numerically higher in patients with higher PD-L1 (Table). Higher TMB (=90th vs. <90th percentile) was not associated with significantly longer OS, or higher LC or RN rates (Table).
Conclusion: Higher PD-L1 tumor expression was associated with improved all-cause mortality. A significant percentage of patients with a very high PD-L1 displayed long-term survival, highlighting the potential importance of multimodality therapy in such patients, and demonstrating that clinicians should be cognizant of treatment-associated long-term toxicities in this population.

Outcomes	OS		LC		RN
PD-L1 groups	Median (mo)	p	2-year % [95%CI]	p	2-year % [95%CI]	p
<1%	11.8 [8.0-17.2]	Ref.	98 [95-100]%	Ref.	5 [2-8]%	Ref.
1-49%	14.4 [12.6-35.3]	0.073	99 [97-100]%	0.54	8 [4-12]%	0.69
50-89%	29.5 [17.0-NR]	0.050	95 [87-100]%	0.53	8 [2-14]%	0.60
=90%	33.1 [17.8-NR]	0.027	98 [100-100]%	1	15 [5-25]%	0.81
TMB
<90th p.	17.7 [14.3-35.3]	Ref.	97 [95-100]%	Ref.	6 [0-12]%	Ref.
=90th p.	NA [17.2-NR]	0.069	97 [92-100]%	0.71	15 [0-30]%	0.93