Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial

Abstract

Purpose: The efficacy of cetuximab is poor in metastatic head and neck squamous cell carcinoma (HNSCC). Cetuximab initiates natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity, with resultant recruitment of immune cells and suppression of anti-tumor immunity. We hypothesized that adding an immune checkpoint inhibitor (ICI) could overcome this and lead to an enhanced anti-tumor response. Patients and Methods: A phase II study of cetuximab and durvalumab in metastatic HNSCC was conducted. Eligible patients had measurable disease. Patients who had received both cetuximab and an ICI were excluded. The primary endpoint was objective response rate (ORR) by RECIST 1.1 at six months. Results: As of April 2022, 35 patients enrolled, of whom 33 received at least 1 dose of durvalumab and were included in the response analysis. Eleven patients (33%) had received prior platinum-based chemotherapy, 10 an ICI (30%), and 1 patient (3%) cetuximab. ORR was 39% (13/33) with a median duration of response of 8.6 months (95% CI: 6.5, 16.8). Median progression-free and overall survivals were 5.8 months (95% CI: 3.7 to 14.1) and 9.6 months (95% CI: 4.8 to 16.3), respectively. There were sixteen grade 3 treatment-related adverse events (TRAEs) and one grade 4 TRAE, with no treatment-related deaths. Overall and progression-free survival did not correlate with PD-L1 status. NK cell cytotoxic activity was increased by cetuximab and further increased with the addition of durvalumab in responders. Conclusions: The combination of cetuximab and durvalumab demonstrated durable activity with a tolerable safety profile in metastatic HNSCC and warrants further investigation.

Multimodality treatment in recurrent/metastatic squamous cell carcinoma of head and neck: current therapy, challenges, and future perspectives

“…A combination of durvalumab and cetuximab was recently evaluated in a single-arm, phase II, non-randomized trial in patients with R/M HNSCC in the second line. ORR, the primary endpoint, was 39%, and the benefit was independent of PD-L1 expression ( 105 ).…”