Data from Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Abstract

<div>AbstractPurpose:<p>A phase II multi-institutional clinical trial was conducted to determine overall survival (OS) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with a combination of cetuximab and nivolumab.</p>Patients and Methods:<p>Patients with R/M HNSCC were treated with cetuximab 500 mg/m<sup>2</sup> i.v. on day 14 as a lead-in followed by cetuximab 500 mg/m<sup>2</sup> i.v. and nivolumab 240 mg i.v. on day 1 and day 15 of each 28-day cycle. Expression of p16 and programmed cell death-ligand 1 (PD-L1) in archived tumors were determined. Tumor-tissue–modified human papillomavirus (TTMV) DNA was quantified in plasma.</p>Results:<p>Ninety-five patients were enrolled, and 88 patients were evaluable for OS with a median follow-up of 15.9 months. Median OS in the 45 patients who had prior therapy for R/M HNSCC (cohort A) was 11.4 months, with a 1 year OS 50% [90% confidence interval (CI), 0.43–0.57]. Median OS in the 43 patients who had no prior therapy (cohort B) was 20.2 months, with a 1-year OS 66% (90% CI, 0.59–0.71). In the combined cohorts, the p16-negative immunostaining was associated with higher response rate (RR; <i>P</i> = 0.02) but did not impact survival while higher PD-L1 combined positive score was associated with higher RR (<i>P</i> = 0.03) and longer OS (log-rank <i>P</i> = 0.04). In the p16-positive patients, lower median (1,230 copies/mL) TTMV DNA counts were associated with higher RR (<i>P</i> = 0.01) and longer OS compared with higher median (log-rank <i>P</i> = 0.05).</p>Conclusions:<p>The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.</p></div>