A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma

Charles Lin,Trang Le,Paul Thomas,Michelle Nottage,Benjamin Chua,Karen Hay,Brett Hughes,Jacqui Keller,Michele Teng,Jennifer Edmunds,Trishna Ballah,Lizbeth Kenny

doi:10.1186/s13014-021-01795-5

Abstract

BackgroundPatients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort.MethodsPatients with unresectable locally and or regionally advanced pathologically confirmed cSCC (stage III-IVa) deemed fit for CRIO by consensus of the Multidisciplinary meeting will be eligible. In the first stage of a two-stage minimax design, we aim to recruit a total of 15 patients. If fewer than 7 patients achieved a complete response in the first stage, we will conclude the treatment is not more effective than standard treatment. The co-primary endpoints of CRIO are the safety of treatment (acute and late toxicities) and the rate of complete response. Secondary endpoints would include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers (CD73, CD39, PD-1, PD-L1) will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET/CT scan will be explored.DiscussionCRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent and adjuvant durvalumab for patients with unresectable stage III-IVa cSCC.Trial registration: Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246)

Highlights

Patients with unresectable advanced cutaneous squamous cell carcinoma are generally treated with palliative intent
We previously demonstrated that in more advanced clinical stage, CD73 expression is increased in cutaneous melanoma patients who did not receive any immunotherapy or BRAF/MEKi
We aim to evaluate if the adenosinergic pathway is present in cutaneous squamous cell carcinoma (cSCC) and its relationship with the Programmed Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) pathway

Summary

Introduction

Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort. A proportion of patients cannot undergo surgery due to significant medical comorbidities which put them at high risk of intraoperative mortalities. This group of patients are categorised to have medically unresectable disease. For the purpose of this study, patients refused to have mutilating surgery and/or residual diseases anticipated due to proximity to critical organs at risk are categorised to have surgically unresectable disease

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