A prospective study of definitive ChemoRadiation with ImmunOtherapy (CRIO) in locally or regionally advanced, unresectable cutaneous squamous cell carcinoma

<h2>ABSTRACT</h2><h3>Background</h3> 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 pilot study of chemoradiation for patients with unresectable cutaneous SCC. The purpose of this study was to evaluate the efficacy and safety of chemoradiation combined with checkpoint inhibitor immunotherapy with durvalumab for this patient cohort. <h3>Methods</h3> Patients with locally advanced and/or nodal metastatic cSCC deemed unsuitable for surgery were treated with definitive radiotherapy to a dose of 70 Gy in 35 fractions, concurrent weekly chemotherapy (cisplatin 40mg/m² or carboplatin AUC 2mg/mL/min) and durvalumab 1500mg every 4 weeks. FDG PET assessment was performed at 19 weeks. 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 complete response and safety. <h3>Results</h3> Fifteen patients were enrolled between May 2019 and June 2021. Fourteen (93%) had regional nodal disease classified as non-metastatic stage IV. Complete response was observed in 9/15 (60%) with no patients undergoing salvage surgery. With a median follow-up of 39 months, all patients who achieved CR were alive without progression or died from another cause. The 6 patients who did not achieve CR all progressed; 5 died due to disease progression and 1 received further systemic therapy. Grade 3 adverse events related to immunotherapy was reported in one patient (7%). The estimated rate of both overall and progression-free survival at 24 months was 65% (95% CI, 35-84). <h3>Conclusions</h3> To our knowledge, 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. The number of serious adverse events was limited.