SBRT Plus Nivolumab in Advanced NSCLC: A Phase II Multicenter Study With Exploratory Bone Metastases Subgroup Analysis.

BACKGROUND: Immune checkpoint blockade provides durable benefit in a subset of patients with advanced non-small-cell lung cancer (NSCLC), but response rates remain limited after progression on standard systemic therapy. Stereotactic body radiotherapy (SBRT) may enhance tumor-antigen release and systemic immune activation, thereby improving the efficacy of PD-1 blockade. This multicenter, single-arm, phase II study evaluated the efficacy and safety of SBRT plus nivolumab in previously treated advanced NSCLC. METHODS: Eighty-three patients who had experienced disease progression after at least one line of standard systemic therapy were enrolled across 9 centers. Patients received SBRT to the primary lung lesion or, in selected cases without a visible primary tumor, to an involved nodal lesion, followed by nivolumab. Patients with symptomatic bone metastases could receive prior bone radiotherapy. The primary endpoint was objective response rate (ORR) according to RECIST version 1.1. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Bone radiotherapy and biomarker analyses were exploratory. RESULTS: The ORR was 39.7% (95% confidence interval [CI], 29.4-51.1%), including complete responses in 10.8%, and the disease control rate was 61.4%. The median duration of response was 27.0 months. Median PFS and OS were 11.1 months and 25.9 months, respectively. Among the 36 patients with bone metastases, the exploratory ORR was 57.2% in those who received bone radiotherapy and 13.6% in those who did not. Elevated baseline alkaline phosphatase and urea levels were associated with poorer survival in exploratory analyses. Treatment-related adverse events occurred in 63.9% of patients, with grade 3-4 events in 4.8% and no treatment-related deaths. CONCLUSIONS: SBRT plus nivolumab demonstrated encouraging and durable antitumor activity with manageable toxicity in previously treated advanced NSCLC. The findings concerning bone radiotherapy and serum biomarkers are exploratory and hypothesis-generating and require validation in prospective randomized studies.