Response-Adapted Surgical and Radiotherapy De-Escalation in Resectable Cutaneous Squamous Cell Cancer Using Pembrolizumab: The De-Squamate Study
Rahul Ladwa, Jenny Lee, Margaret McGrath, Caroline Cooper, Howard Liu, James Bowman, Ruta Gupta, Claire Cuscaden, Michelle Nottage, Jonathan R. Clark, Dieu Le, Marketa Pauley, Arutha Kulasinghe, Jazmina L. Gonzalez Cruz, Sandro Porceddu, Brett Hughes, Benedict Panizza
Abstract
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.