Supplementary Figures 7A, 7B and 7C Cetuximab enhances anti-tumor cytokines: Cytokine concentrations in the sample supernatants were determined by enzyme-linked immunosorbent assay (ELISA) using a Luminex assay (R&Dsystems, a bio-techne brand, Minneapolis, MN) according to the manufacturer's protocol. Cetuximab alone decreased pro-tumorigenic IL-6 levels and increased IP-10 suggesting an anti-tumor response (Supplementary Figure 7A and 7B); however, these cytokines were not significantly changed between responders (those with CR, PR, SD) and non-responders. The full panel of tested cytokines, shown in Supplementary Figure 7C.Abbreviations: CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; NK: Natural Killer; IL: interleukin; IP: Interferon gamma inducible protein-10 (IP-10).
ARTICLE ABSTRACT
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.
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.
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.
The combination of cetuximab and durvalumab demonstrated durable activity with a tolerable safety profile in metastatic HNSCC and warrants further investigation.
