A Randomized Phase 2 Trial of Nivolumab and Stereotactic Ablative Body Radiation Therapy in Advanced Non-Small Cell Lung Cancer, Progressing After First- or Second-Line Chemotherapy (NIVORAD)
- Author(s)
- Kothari, G; O'Byrne, KJ; Brown, C; Stockler, MR; Walker, M; Hardcastle, N; Kron, T; Le, HV; Kosmider, S; Cameron, L; Lao, L; Mitchell, P; Siva, S;
- Journal Title
- International Journal of Radiation Oncology, Biology, Physics
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: Programmed cell death protein-1 inhibitors have improved metastatic non-small cell lung cancer (NSCLC) prognosis. Stereotactic ablative body radiation therapy (SABR) may enhance immunity. This study evaluated the activity and safety of adding SABR to first-line immunotherapy post chemotherapy with nivolumab for metastatic NSCLC. METHODS AND MATERIALS: NIVORAD (ALTG14/002/CT0135/TROG 16.01) randomized adults (1:2) to nivolumab 240 mg 2-weekly until disease progression or prohibitive toxicity either alone, or with single fraction SABR (18-20 Gy). Eligible patients had metastatic NSCLC, had progressed after 1-2 lines of chemotherapy, were immunotherapy-naïve, and had a disease site suitable for SABR. The primary endpoint was progression free survival (PFS) at 6 months. Secondary endpoints were objective tumor response rate, overall survival, PFS at 1 and 2 years, and adverse events (AEs). The planned sample size of 120 was to provide 80% power with a 1-sided type 1 error rate of 5% to distinguish the observed proportions alive and progression free at 6 months. The study closed early because of slow accrual. RESULTS: Fifty participants were recruited and randomly assigned to nivolumab alone (n = 16) or nivolumab plus SABR (n = 34). Baseline characteristics were balanced across treatment arms, apart from percentage of females which was higher in the control arm (56% vs 35%). Median follow-up was 26 months. PFS was similar among those assigned nivolumab plus SABR versus nivolumab alone (PFS at 6 months 49% vs 44%, hazard ratio [HR], 0.68; 95% CI, 0.36-1.27; P = .23). Objective tumor response rate (8/34[24%] vs 4/16[25%]) and overall survival (HR, 0.86; 95% CI, 0.43-1.75; P = .69) were also similar in the 2 treatment groups. Rates of serious grade 3-5 AE (12/16 (75%) vs 24/31 (77%) in experimental arm) were also similar in the 2 groups. There were 2 deaths, 1 in each treatment group (pneumonitis and respiratory failure). CONCLUSIONS: Nivolumab plus SABR demonstrated similar efficacy and safety to nivolumab alone in metastatic NSCLC progressing after chemotherapy, without increased AEs.
- Department(s)
- Radiation Oncology; Physical Sciences
- Publisher's Version
- https://doi.org/10.1016/j.ijrobp.2025.12.021
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-22 02:13:25
Last Modified: 2026-01-22 02:13:47