Avelumab plus cetuximab in patients with unresectable stage III or IV cutaneous squamous cell carcinoma: clinical activity and safety results from AliCe, a single-arm multicentre phase II DeCOG trial.

Abstract

In cutaneous squamous cell carcinoma (cSCC), programmed cell death protein 1 (PD-1) and epidermal growth factor receptor (EGFR) inhibitors are effective in a considerable proportion of patients. However, there is an unmet medical need for patients with perianogenital cSCC or cSCC refractory to PD-1 therapy. To evaluate the combination avelumab (programmed death ligand 1 inhibitor) and cetuximab (EGFR inhibitor) in people with advanced cSCC treated for up to 1 year. This multicentre phase II trial enrolled patients with advanced cSCC (prior systemic therapy allowed) to receive avelumab (10 mg  kg-1 Q2W) plus cetuximab (500 mg m-2 Q2W) for up to 1 year. The primary endpoint was objective response. Predefined subgroups were line of therapy and localization of the primary tumour (perianogenital/other locations). Of 52 enrolled patients, 49 received at least 1 treatment dose. Of these patients, 20 achieved an objective response [41%, 95% confidence interval (CI) 27-56; 9 partial responses/11 complete responses (CRs)]. While treatment-naïve patients (n = 35) achieved a higher objective response rate (46%, 95% CI 29-63) than those who were pretreated (29%, 95% CI 8-58), 4 of 14 pretreated patients experienced an objective response, 2 with prior PD-1 inhibition. Five of 14 patients with perianogenital cSCC achieved an objective response (36%, 95% CI 13-65), including 4 CRs. At a median follow-up of 35 months, median progression-free and overall survival were 8.4 and 23.1 months, respectively. Grade 1 and 2 treatment-related adverse events (TRAEs) were common, while grade ≥ 3 events occurred in only 10 patients (20%) and 7 experienced serious TRAEs (14%); 2 discontinued treatment due to drug-related toxicity. Notably, quality of life improved, especially in patients with perianogenital primaries. Avelumab in combination with cetuximab demonstrates encouraging clinical activity in advanced cSCC, including patients with challenging subgroups such as perianogenital primaries or those with disease that has progressed on anti-PD-1 monotherapy. This is especially true when patients are carefully selected for their ability to undergo treatment for at least 12 weeks.