A phase II randomized trial of nivolumab with stereotactic body radiotherapy (SBRT) versus nivolumab alone in metastatic (M1) head and neck squamous cell carcinoma (HNSCC).

Abstract

6009 Background: A minority of patients with metastatic HNSCC respond to the anti-programmed death (PD-1) monoclonal antibody, Nivolumab (Nivo). We sought to determine whether targeted radiation to a single lesion combined with Nivo would enhance tumor regression in non-irradiated lesions (abscopal response) and improve outcomes. Methods: Patients with M1 HNSCC (including nasopharynx) with at least two RECIST 1.1 measurable lesions were randomized with stratification for viral status (EBV/HPV pos vs. neg) 1:1 to either Nivo alone q 2 weeks or Nivo with SBRT to a single lesion (9 Gy x 3) between the 1st and 2nd doses of Nivo. The primary end-point was objective response rate (ORR) in non-irradiated lesions using RECIST 1.1. Secondary analyses included overall survival (OS), progression free-survival (PFS), and duration-of-response (DOR). We hypothesized that SBRT added to Nivo would increase ORR from 15% to 45%. Enrolling 53 patients thus provides a one-sided alpha of 0.10 and a power of 0.80. Results: 53 patients were randomized, 26 to Nivo alone and 27 to Nivo+SBRT; the lung was the most common irradiated site (59%). There were no significant differences between arms in terms of age (p = 0.12), viral status (pos vs neg; p = 0.786), primary site (oropharynx vs. nasopharynx vs other; p = 1.0), or median lines of prior chemotherapy (1; p = 0.73). ORR in the Nivo alone arm was 26.9% (95% CI: 13.7, 46.1%) vs 22.2% (95% CI: 10.6%, 40.8%) in the Nivo+SBRT arm (p = 0.94). Median DOR with Nivo alone was not reached (NR) vs 9.3 months (95% CI: 5.52, NR) with Nivo+SBRT (p = 0.21). Median follow-up amongst surviving patients was 12.8 mos; OS at 1 year was 64% (95% CI: 47%, 88%) in the Nivo alone arm vs 53% (95% CI: 36%, 79%) in the Nivo+SBRT arm (p = 0.79); median PFS was 1.9 mos (95% CI: 1.78, NR) with Nivo vs 2.4 mos (95% CI: 1.0, 11.4) with Nivo+SBRT (p = 0.8). Treatment-related ≥ Grade 3 toxicities in the Nivo alone vs Nivo+SBRT arms occurred in 15% vs. 11% of patients (p = 0.96). Conclusions: While safe, the addition of SBRT to Nivo in M1 HNSCC failed to improve ORR, PFS, or OS. This is the first randomized evaluation of the abscopal response in any tumor histology. Biomarker analyses are near completion. Clinical trial information: 02684253.