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

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. Experimental Design: Patients with R/M HNSCC were treated with cetuximab 500 mg/m2 IV Day (D) -14 as a lead-in followed by cetuximab 500 mg/m2 IV and nivolumab 240 mg IV on D1 and D15 of each 28-D 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% 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, median (log-rank p=0.05). Conclusion: The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.

Efficacy of cetuximab plus PD-1 inhibitor differs by HPV status in head and neck squamous cell carcinoma: a systematic review and meta-analysis

“… 1–3 5 6 10 11 13 The study characteristics are described in table 1 . The primary endpoint was the ORR in two phase 1b and two phase 2 trials, 2 3 10 13 1-year OS rate in one phase 2 trial (two cohorts), 11 and OS in two phase 3 trials. 1 6 HPV status was mostly assessed by p16 immunohistochemistry in all the trials.…”

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

“… 422 Therefore, the TPEx regime can be a reliable alternative to the PCF regime in the first-line treatment of R/M-HNSCC patients. In addition to chemotherapy, cetuximab combined with the CDK4/6 inhibitor palbociclib, 423 VEGF monoclonal antibody bevacizumab, 424 or immunotherapy (pembrolizumab 425 and nivolumab 426 ) also showed promising clinical activity and safety profiles in R/M-HNSCC patients, including platinum-resistant and cetuximab-resistant patients.…”

Current perspectives on recurrent HPV-mediated oropharyngeal cancer

“…For patients with unresectable disease or who are unable to undergo surgical resection, re-irradiation with or without chemotherapy is an option that has historically demonstrated limited benefit for non-nasopharyngeal sites, and carries high rates of toxicity ( 35 , 61 ). Trials combining chemotherapy with hyper-fractionated reirradiation for recurrent head and neck cancer had fairly low overall survival (15.2% at two years), although patients with longer disease free interval had better outcomes ( 84 ). Advancements in radiation therapy technology have improved outcomes.…”