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).

Abstract

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. 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. 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). Nivolumab plus SABR demonstrated similar efficacy and safety to nivolumab alone in metastatic NSCLC progressing after chemotherapy, without increased AEs.