Anti-EGFR plus anti-PD1 in advanced and refractory cutaneous squamous cell carcinoma: a cohort study

Advanced cutaneous squamous cell carcinoma (cSCC) is associated with a poor prognosis. Although anti-Programmed cell Death protein 1 (anti-PD1) immunotherapy has improved cSCC management, its efficacy remains limited in some patients. Second-line options, including anti-epidermal growth factor receptor (anti-EGFR) antibodies and chemotherapies, exhibit transient efficacy and often good tolerability. Given the lack of successive treatment lines, new strategies are emerging, such as the combination of anti-PD1 and anti-EGFR agents.

We conducted a retrospective, monocentric cohort study including patients treated in our oncodermatology department between 2013 and 2024 for advanced cSCC refractory to anti-PD1 monotherapy and who received a combination of anti-PD1 and anti-EGFR as second- or third-line therapy. The aim was to assess the efficacy and safety of this combination.

Fourteen patients were included, predominantly male (12/14), with a median age of 63 years. Most tumors originated from head and neck primary sites (n = 8). Eleven patients had progressed after prior exposure to both anti-PD1 therapy and cetuximab combined with chemotherapy. Thirteen patients received cetuximab (500 mg/m2) combined with pembrolizumab every 3 weeks, and 1 received cetuximab with nivolumab. The overall response rate was 38.5%, including 15.5% complete and durable response after treatment discontinuation, observed at 9 and 16 months, and 23% partial responses. Responses occurred early, with subsequent deepening observed in 2 patients. Adverse events were mainly grade 1, and only 2 cases experienced grade 3 toxicity (acneiform rash).

In a heavily pretreated real-life population with advanced cSCC, the anti-PD1/anti-EGFR combination showed clinical activity with acceptable safety, supporting its role as later-line strategy.