Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma

TLDR

Anti‑PD‑1 monotherapy yields only modest objective response rates in metastatic or recurrent head and neck squamous cell carcinoma. The study tested whether adding stereotactic body radiotherapy to nivolumab would synergistically enhance response via an abscopal effect in a randomized phase II trial. Sixty‑two patients with at least two metastatic lesions were randomized 1:1, stratified by HPV status, to receive nivolumab alone or nivolumab plus SBRT (9 Gy × 3) to one lesion, with the primary endpoint being objective response in non‑irradiated lesions per RECIST and safety assessed per protocol. The addition of SBRT did not improve objective response (34.5 % vs 29.0 %, P = 0.86), overall survival, progression‑free survival, or response duration, and grade 3‑5 toxicities were similar, indicating no abscopal effect in unselected metastatic HNSCC patients.

Abstract

The objective response rate (ORR) for single-agent anti-programmed death receptor 1 (anti-PD-1) therapy is modest in patients with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). We aimed to test whether radiotherapy may act synergistically with anti-PD-1 therapy to improve response through the abscopal effect.We conducted a single-center, randomized, phase II trial of nivolumab (anti-PD-1 therapy) versus nivolumab plus stereotactic body radiotherapy (SBRT) in patients with metastatic HNSCC. Patients had at least two metastatic lesions: one that could be safely irradiated and one measurable by RECIST version 1.1. Patients were randomly assigned (1:1), stratified by human papillomavirus status, to nivolumab (3 mg/kg intravenously every 2 weeks) or nivolumab (same dose) plus SBRT (9 Gy × 3) to 1 lesion. The primary end point was ORR in nonirradiated lesions, which was assessed by RECIST in patients with at least one available set of on-treatment images; safety was assessed in a per-protocol population.Between March 11, 2016, and June 22, 2018, 62 patients were randomly assigned to nivolumab (n = 30) or nivolumab plus SBRT (n = 32). There was no statistically significant ORR difference between arms (34.5% [95% CI, 19.9% to 52.7%] v 29.0% [95% CI, 16.1% to 46.6%]; P = .86). There was no significant difference in overall survival (P = .75), progression-free survival (P = .79), or response duration (P = .26). Grade 3-5 toxicities were similar (13.3% v 9.7%; P = .70).We found no improvement in response and no evidence of an abscopal effect with the addition of SBRT to nivolumab in unselected patients with metastatic HNSCC.