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 antitumor immunity. We hypothesized that adding an immune-checkpoint inhibitor (ICI) could overcome this and lead to an enhanced antitumor 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 6 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% confidence interval (CI): 6.5–16.8]. Median progression-free and overall survivals were 5.8 months (95% CI: 3.7–14.1) and 9.6 months (95% CI: 4.8–16.3), respectively. There were 16 grade 3 treatment-related adverse events (TRAE) 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.

Opioid misuse has substantial consequences for individuals and society. Deaths associated with drug overdoses have doubled in the last decade, with 70 200 overdose-related deaths reported in the United States in 2017.¹ In 2016, 40% of the opioid-related overdose deaths were associated with the use of prescription opioids.² Ohio has been particularly devastated by the opioid crisis. Between 2015 and 2017, Ohio had the second highest number of opioid-related deaths among all states.^3,4 The death rate related to unintentional drug poisonings in Ohio, which is largely associated with opioid-related overdose, increased by 1081% between 2000 and 2017.⁵