279 - Combined Stereotactic Radiotherapy and Immunotherapy Improves Survival in Driver-Gene-Negative NSCLC Patients with Brain Oligometastases: A Phase II Observational Clinical Study

01:20pm - 01:30pm ET

Room 156

Presenter(s)

Xiaomei Gong, MD, PhD - ShangHai pulmonary hospital, ShangHai, Shanghai

X. Gong¹, S. Luo², P. Zhu³, J. Pang³, and P. Li⁴; ¹Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China, ²Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China, ³Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China, ⁴Shanghai Pulmonary Hospital,Department of Radiation Oncology, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai,, Shanghai, Shanghai, China

Purpose/Objective(s):

This study aimed to evaluate the efficacy and safety of stereotactic radiosurgery (SRT) combined with immune checkpoint inhibitors (ICIs) and chemotherapy (ChT) for treating brain oligo-metastases (BMs) in driver-gene-negative non-small cell lung cancer (NSCLC).

Materials/Methods:

In this prospective, multicenter, phase II observational study, 87 NSCLC patients with 1–3 brain metastases were divided into two groups: SRT+ ICIs+ChT(n=45) and ICIs +ChT (n=42). Outcomes were overall survival (OS), intracranial progression-free survival (iPFS), progression-free survival (PFS), and intracranial objective response rate (iORR). The association between hematologic markers—hemoglobin (Hb) and absolute lymphocyte count (ALC)—and prognosis was also analyzed.

Results:

Compared with the ICIs+ChT group, the SRT+ICIs+ChT group showed significantly improved iPFS (17.30% vs. 12.33%,p=0.005) and PFS (9.97 vs. 7.83 months, p=0.008). In the subgroup with brain metastases =0.5 cm³, the SRT+ICIs+ChT group demonstrated superior outcomes across multiple endpoints: OS (28.2 vs. 14.5 months, p=0.003), iPFS (17.3 vs. 11.8 months), and iORR (50.0% vs. 37.5%). A significant OS benefit was also observed in symptomatic patients (11.7 vs. 4.7 months, p=0.002). Among patients receiving SRT+ICIs+ChT therapy, concurrent administration (initiated within 2–4 weeks after SRT) was associated with longer OS (43.9 vs. 17.2 months) and PFS (21.8 vs. 9.3 months), as well as higher iORR and intracranial disease control rate, compared to sequential treatment. Hematologic analysis identified baseline Hb >100 g/L (HR 0.080, 95% CI 0.028–0.226, p<0.001) and ALC >0.6×10?/L (HR 0.143, 95% CI 0.041–0.507, p=0.003) as independent favorable prognostic factors for OS. The combination therapy did not increase the incidence of central nervous system or immune-related adverse events.

Conclusion:

For patients with driver-gene-negative NSCLC brain metastases, Concurrent SRT-ICI-ChT synergistically improves survival outcomes and intracranial disease control. This effect is particularly pronounced in symptomatic patients or those with larger metastatic lesions (=0.5 cm³). Additionally, baseline Hb > 100 g/L and ALC > 0.6 × 10?/L were identified as favorable prognostic hematologic markers. The combination regimen was well tolerated without increased toxicity. These findings support the integration of stereotactic radiosurgery and immunotherapy in the comprehensive management of NSCLC brain metastases.