Response-Adapted Surgical and Radiotherapy De-Escalation in Resectable Cutaneous Squamous Cell Cancer Using Pembrolizumab: The De-Squamate Study

PURPOSE: The high rates of pathologic complete response (pCR) after neoadjuvant immunotherapy have generated interest for a risk adaptive surgical and radiotherapy-free management approach to reduce morbidity in resectable cutaneous squamous cell carcinoma (cSCC). METHODS: We conducted a phase II, multicenter study to evaluate pembrolizumab in patients with resectable stage II-IV (M0) cSCC. Patients received pembrolizumab, administered at a dose of 200 mg once every 3 weeks for four cycles, before undergoing a 18F-labeled fluorodeoxyglucose-positron emission tomography assessment. Patients who achieved a clinical complete response (cCR), defined as a complete metabolic response and negative mapping biopsies of the target site(s), avoided planned surgery and radiotherapy (total de-escalation). In the absence of a cCR, patients underwent surgery with the recommendation of omitting adjuvant radiotherapy (partial de-escalation) on the basis of a pCR. Patients proceeded to 13 additional cycles of maintenance pembrolizumab. The primary end point of a clinical or pathologic complete response (cpCR) was the combined rate of cCR and pCR. Key secondary end points included omission of surgery ± radiotherapy, event-free survival, and adverse events (AEs). RESULTS: A total of 27 patients received pembrolizumab. A cpCR was observed in 17 patients (63% [95% CI, 42 to 80), composed of a pCR in four (15%) and a cCR in 13 (48%). Total and partial de-escalation was achieved in 48% and 15%, respectively. With a median follow-up of 18 months, no recurrence was seen in those patients with a cpCR. Treatment-related AEs of grade ≥3 were observed in two patients (7%). There were no treatment-related deaths. CONCLUSION: Pembrolizumab led to a high rate of cpCR in resectable cSCC and demonstrated the potential to avoid surgery and radiotherapy.