Cemiplimab in a very frail population of patients with advanced or metastatic cutaneous squamous cell carcinoma: A monocenter real-life experience from Italy.
Authors: Guida Michele , Fanizzi Annarita , Quaresmini Davide , Nardone Annalisa , Armenio Andrea , Montagna Elisabetta Sara , Sciacovelli Angela Monica , Massafra Raffaella , De Risi Ivana , Albano Anna , Strippoli Sabino 
Published: June 2021

e21524 Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Although representing less than 5% of all CSCCs, advanced stages are difficult to treat. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy in the US and EU for patients with locally advanced (laCSCC) or metastatic (mCSCC) CSCC. Phase I-II studies showed high antitumor activity and good tolerability, but few data are still available regarding cemiplimab in real life experience in non-selected patients. Methods: We recruited 30 consecutive patients with laCSCC (25 pts) and mCSCC (5 pts) treated with cemiplimab from August 2019 to November 2020 at our Institution. Median age was 81 years (range 36-95); 24 males; median ECOG PS 1 (range 0-2). Five patients had an immunosuppressive condition including 3 patients with stable hematologic malignancies and two patients on immunosuppressive therapy for kidney transplantation and Crohn’s disease, respectively. The majority of patients had comorbidities (median 3). Cemiplimab was administered at the flat dose of 350 mg i.v. every 21 days until disease progression or unacceptable toxicity. In all patients we evaluated clinical outcomes, toxicity, and associations between clinical outcomes and peripheral blood parameters. Results: We reported 23 responses (ORR 76.7%) with CR in 5 patients (16.7%). One patient had SD for 5 months. The global DCR was 80%. The median duration of response and PFS was not reached at a median follow-up of 6 months. We observed a higher ORR in head and neck primary tumours (87% vs. 42.9% of others, p = 0.016) and in patients with haemoglobin level > 12 g/dL (87.5% vs. 64.3%). No significative difference in ORR was observed with respect to the median age (81.3% in >81 years vs. 71.4% in < 81 years). Among the 5 patients with immunosuppressive status, a response was obtained in 4 patients (80%), including 1 CR. Nine patients died, 7 for PD and 2 for causes unrelated to the disease. Twenty patients (67.7%) still have an ongoing response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in 7 patients (23.3%) and skin toxicity in 10 patients (33.3%) including pruritus in 6 patients, rash in 3 patients, bullous erythema in 1 patient. Only 3 (10%) patients experienced severe (grade 3/4) toxicity. Three responder patients interrupted treatment (2 for toxicity after 7 and 9 cycles, and one for pre-existing dementia) but maintaining their response. Conclusions: In our real-life experience cemiplimab showed high antitumor activity with acceptable safety profile similar to those in selected patients of trials. Moreover, its antitumor activity resulted not impaired in very elderly patients or in those with immunocompromized status.