Background
There is limited prospective data to guide the management for patients with cutaneous squamous cell carcinoma (cSCC) presenting with locally advanced, unresectable disease. Previously we conducted a prospective study of chemoradiation (CRT) for patients with unresectable cSCC (1). The purpose of this study was to evaluate the efficacy and safety of CRT combined with checkpoint inhibitor immunotherapy with durvalumab for this patient cohort.
Methods
Patients with locally advanced or nodal metastatic cSCC deemed unsuitable for surgery, by a multidisciplinary clinic, were treated with definitive RT (70 Gy in 35 fractions), concurrent weekly chemotherapy (cisplatin 40mg/m2 or carboplatin AUC 2mg/mL/min) and durvalumab 1500mg every 4 weeks, starting on the first week of CRT. Assessment was performed at 19 weeks, after 5 cycles of durvalumab. Patients who achieved a complete response (CR) did not receive further treatment. Patients with residual, but not progressive, disease could continue durvalumab for a further 6 cycles, with or without salvage surgery. Primary endpoints were CR and safety.
Results
Fifteen patients were enrolled between May 2019 and June 2021. Fourteen (93%) had regional nodal disease classified as non-metastatic stage IV. CR was observed in 9/15 (60%) with no patients undergoing salvage surgery. All patients who achieved CR were alive without progression or died from another cause at data cutoff, with median follow-up of 39 months (26-44). The 6 patients who did not achieve CR all progressed; 5 died due to disease progression and 1 received further systemic therapy on a clinical trial. Grade 3 adverse events related to immunotherapy was reported in one patient (7%).
Conclusions
This is the only prospective series of chemoradiation in combination with checkpoint inhibitor immunotherapy for unresectable cSCC. A high CR rate was achieved and responses were durable. No unexpected adverse events were identified.