Multicenter phase 2 trial of response-adapted surgery and radiotherapy de-escalation after neoadjuvant pembrolizumab in resectable cSCC

The high rates of pathologic complete response after neoadjuvant immunotherapy have generated interest for a risk adaptive surgery-free and radiotherapy-free management approach to reduce morbitidy in resectable cutaneous squamous cell carcinoma (cSCC). The multicenter phase 2 De-Squamate Study in Australia included cSCC patients who received four cycles of neoadjuvant pembrolizumab and subsequently underwent FDG-PET assessment. Patients with clinical complete response avoided planned surgery and radiotherapy (‘total de-escalation’) and patients without complete response underwent surgery and in case of pathologic complete response avoided planned radiotherapy (‘partial de-escalation’). Total de-escalation was achieved in 48% of patients and partial de-escalation in 15%. With a median follow-up of 18 months, no recurrence was seen in patients with total or partial de-escalation. Treatment-related adverse events of grade 3 or 4 were observed in 7%; there were no grade 5 TRAEs. The authors conclude that neoadjuvant pembrolizumab demonstrated the potential for de-escalation of treatment in cSCC,