A Randomized Phase 2 Trial of Nivolumab and Stereotactic Ablative Body Radiotherapy (SABR) in Advanced Non-Small Cell Lung Cancer, Progressing After First- or Second-Line Chemotherapy (NIVORAD)
Mené sur 50 patients atteints d'un cancer métastatique du poumon non à petites cellules ayant progressé après 1 à 2 lignes de chimiothérapie (durée médiane de suivi : 26 mois), cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression à 6 mois, d'une immunothérapie par nivolumab en combinaison ou non avec une radiothérapie stéréotaxique d'ablation
Purpose: PD-1 inhibitors have improved metastatic non-small cell lung cancer (NSCLC) prognosis. Stereotactic ablative body radiotherapy (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 240mg 2-weekly until disease progression or prohibitive toxicity either alone, or with single fraction SABR(18-20Gy). 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 (OTRR), overall survival (OS), 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 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%, HR=0.68, 95%CI 0.36-1.27, p=0.23). OTRR (8/34[24%] vs 4/16[25%]) and OS (HR=0.86, 95%CI 0.43–1.75, p=0.69) were also similar in the two treatment groups. Rates of serious Grade 3 to 5 AE (12/16 (75%) vs 24/31 (77%) in experimental arm) were also similar in the two groups. There were two deaths, one in each treatment group (pneumonitis and respiratory failure).
Conclusion: Nivolumab plus SABR demonstrated similar efficacy and safety to nivolumab alone in metastatic NSCLC progressing after chemotherapy, without increased AEs.
International Journal of Radiation Oncology, Biology, Physics , résumé, 2026