3568 - Optimal Sequencing of Immunotherapy and Radiotherapy in Driver Gene-Negative NSCLC with Brain Metastases: A Real-World IPTW Analysis
Presenter(s)
E. Munai1, W. Zhou2, Z. Tang3, L. Wang2, and Y. Wu2; 1Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China, Chongqing, China, 2Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China, 3Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, China
Purpose/Objective(s): The integration of immune checkpoint inhibitors (ICIs) with radiotherapy (RT) has transformed the management of non-small cell lung cancer (NSCLC) with brain metastases (BMs). However, the optimal temporal sequencing of these modalities remains a critical clinical uncertainty. We aimed to evaluate whether the timing of immunotherapy (I) relative to intracranial radiotherapy (RT) influences survival and intracranial control in patients with driver gene–negative NSCLC.
Materials/Methods: This retrospective cohort study analyzed 158 patients with driver gene–negative NSCLC and BMs receiving their first course of intracranial RT (SRT or WBRT). Patients were categorized by I sequence: Be-RT (I initiated within 3 months before RT, n=104) and Af-RT (I initiated within 3 months after RT, n=54). To address baseline imbalances, Inverse Probability of Treatment Weighting (IPTW) was employed to balance 14 covariates, including age, KPS, BM count, and RT modality. Primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS).
Results: The median follow-up was 22.6 months. Before weighting, the Af-RT group demonstrated significant advantages in median OS (33.4 vs. 19.7 months, P = 0.002) and iPFS (17.9 vs. 9.5 months, P = 0.004) compared to the Be-RT group. After IPTW adjustment, the survival benefit of the Af-RT sequence remained statistically significant for both OS (adjusted median 29.7 vs. 19.7 months, P = 0.012) and iPFS (adjusted median 17.8 vs. 9.5 months, P = 0.034). IPTW-adjusted multivariable Cox regression confirmed that I sequence was an independent prognostic factor for OS (P = 0.001) and iPFS (P = 0.004). Other independent predictors included RT modality (SRT vs. WBRT) and prior thoracic treatment.
Conclusion: For driver-gene-negative NSCLC with BMs, initiating immunotherapy after the Af-RT yields significantly superior OS and iPFS compared to pre-RT initiation. These findings suggest that the initial RT course may prime the tumor microenvironment for subsequent ICI efficacy. Our results support the use of the Af-RT sequence in primary treatment planning to optimize clinical outcomes.