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

• Type of Material: Article
• Authors: Christine H Chung, Moffitt Cancer Center, Tampa; Jiannong Li, Moffitt Cancer Center, Tampa; Conor Steuer, Emory University; Priyanka Bhateja, Ohio State University; Matthew Johnson, Moffitt Cancer Center, Tampa; Jude Masannat, Moffitt Cancer Center, Tampa; Maria I Poole, Moffitt Cancer Center, Tampa; Feifei Song, Moffitt Cancer Center, Tampa; Juan C Hernandez-Prera, Moffitt Cancer Center, Tampa; Helen Molina, Moffitt Cancer Center, Tampa; Bruce M Wenig, Moffitt Cancer Center, Tampa; Sunil Kumar, Naveris Inc; Charlotte Kuperwasser, Naveris Inc; Philip J Stephens, Naveris Inc; Joaquim M Farinhas, Moffitt Cancer Center, Tampa; Dong Shin, Emory University; Julie A Kish, Moffitt Cancer Center, Tampa; Jameel Muzaffar, Moffitt Cancer Center, Tampa; Kedar Kirtane, Moffitt Cancer Center, Tampa, Florida; James W Rocco, Ohio State University; Michael J Schell, Moffitt Cancer Center, Tampa; Nabil Saba, Emory University; Marcelo Bonomi, Ohio State University
• Language: English
• Date: 2022-06-01
• Publisher: AMER ASSOC CANCER RESEARCH
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022, American Association for Cancer Research
• Final Published Version (URL): http://dx.doi.org/10.1158/1078-0432.CCR-21-3849
• Title of Journal or Parent Work: CLINICAL CANCER RESEARCH
• Volume: 28
• Issue: 11
• Start Page: 2329
• End Page: 2338
• Keywords: COMBINATION; MULTICENTER; PEMBROLIZUMAB; PLUS CETUXIMAB; HUMAN-PAPILLOMAVIRUS; Oncology; CYTOTOXICITY; RISK; CANCER; OPEN-LABEL; PLATINUM-BASED CHEMOTHERAPY; Life Sciences & Biomedicine; Science & Technology

Abstract

Purpose: 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. Patients and Methods: Patients with R/M HNSCC were treated with cetuximab 500 mg/m2 i.v. on day 14 as a lead-in followed by cetuximab 500 mg/m2 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. Results: 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; P = 0.02) but did not impact survival while higher PD-L1 combined positive score was associated with higher RR (P = 0.03) and longer OS (log-rank P = 0.04). In the p16-positive patients, lower median (1,230 copies/mL) TTMV DNA counts were associated with higher RR (P = 0.01) and longer OS compared with higher median (log-rank P = 0.05). Conclusions: The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.