Long-term survival after anti-PD-1 discontinuation in advanced cutaneous squamous cell carcinoma (cSCC): a proof of concept of benefit of concomitant cemiplimab and radiotherapy.

BACKGROUND: In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation. METHOD: We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab. RESULTS: Of the 12 patients with a partial or complete response, we report 8 (66.7%) persistent responses 2 years after stopping cemiplimab, with only 2 patients progressing to distant disease, one lost to follow-up, and one death a priori unrelated to the disease. CONCLUSION: Our study confirms a long-term and persistent effect despite discontinuation of cemiplimab at least up to 2 years later.

Real-Life Study of the Benefit of Concomitant Radiotherapy with Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma (cSCC): A Retrospective Cohort Study.

BACKGROUND: Cemiplimab is a monoclonal antibody targeting the PD-1, and phase II trials have shown its efficacy in the treatment of advanced cutaneous squamous cell carcinoma in patients who are not candidates for curative surgery or radiation therapy as a first- or later-line treatment. A synergistic antitumoral response has been demonstrated with concurrent radiotherapy and PD1-immunotherapy. However, no real-life study has demonstrated this effect in advanced cutaneous squamous cell carcinoma. METHODS: We conducted a real-life retrospective cohort study to investigate the benefit of concomitant therapy in 33 patients treated with cemiplimab at the University Hospital of Caen, alone (C group) or concomitant to radiotherapy (C/RT group). Our primary objectives were to evaluate the best overall response and objective response rate. Our secondary objectives were the disease control rate, median time to response, progression-free survival, overall survival, clinical benefit of radiotherapy, and safety data. After stopping cemiplimab administration, we performed a follow-up of our patients and performed a descriptive study. RESULTS: We reported an objective response rate of 45.5%, including 47.6% in the cemiplimab group versus 41.6% in the concomitant group. The addition of radiotherapy to cemiplimab enables an earlier clinico-radiological response, with a median duration of 5.5 months in the cemiplimab group versus 3 months in the concomitant therapy group. The response to treatment was prolonged despite discontinuation of cemiplimab, with 91.6% (n = 11/12) and 83.3% (n = 10/12) patients in complete or partial remission at 6 months and 1 year after cessation of cemiplimab and no switch to another oncological treatment, respectively. Radiation therapy also provided a therapeutic effect in 83.3% of the patients in the concomitant group, without increasing the occurrence of adverse events. CONCLUSIONS: Our study confirms the efficacy of cemiplimab and radiotherapy in the management of advanced cutaneous squamous cell carcinoma. Concomitant therapy permitted to obtain an earlier radiological response, a beneficial local therapeutic effect of radiotherapy, without any safety alert.