Anti-EGFR combined with anti-PD1 in refractory locally advanced or metastatic cutaneous squamous cell carcinoma

Background: Although the prognosis for advanced cutaneous squamous cell carcinoma (CSCC) has changed since immunotherapy, some patients have primary or secondary resistance to anti-PD1.Therapeutic strategies are emerging that combine anti-PD1 with other molecules, in order to potentiate their efficacy.Methods: We report a single-centre series of 14 patients who received the anti-EGFR/anti-PD1 combination.The aim was to describe the efficacy and safety of this combination.Results: The 14 patients were aged on average 66 years (39 to 85 years), with a predominance of head and neck CEC (8/14).There were 9 patients with lymph node involvement, 3 with visceral metastases, 1 with locally advanced disease and 1 with multiple CSCC.All had received prior anti-PD1 therapy and 11 had received cetuximab/carboplatin.The treatment regimen was cetuximab + pembrolizumab /3 weeks, except for 1 patient who received cetuximab/nivolumab.One patient discontinued treatment after 1 course due to poor tolerance, with no evaluable efficacy.Of the 13 evaluable patients, there were 2 complete and prolonged responses to treatment discontinuation (15%), 3 partial responses (23%), 3 stable responses (23%) and 2 dissociated responses between skin and lymph node involvement (15%).Three patients progressed from the outset (23%), but 1 of them nevertheless benefited from a slowing of the progression and then a clean surgery procedure, leading finally to a persistent complete response (Figure 1).Adverse events were expected and mainly grade 1.The most frequent were: rash acneiform (9/14), plantar fissures (3/14), hypomagnesemia (3/14), lymphopenia (3/14) and immuno-induced corticotropic insufficiency (3/14).Conclusions: The combination of anti-EGFR and anti-PD1 appears to be of benefit in cases of primary or secondary resistance in advanced head and neck cancer CSCC, with a good safety profile, pending the results of phase II studies.