Abstract
BackgroundModified docetaxel, cisplatin, and 5-fluorouracil (mDCF) regimen has become a new standard for the treatment of metastatic or unresectable locally advanced recurrent squamous cell carcinoma of the anus (SCCA) after demonstrating improved efficacy (12-month PFS of 47%) in the Epitopes-HPV02 trial. Antibodies targeting the checkpoint inhibitor (CKI) programmed cell death protein-1 (PD1) have demonstrated the efficacy as monotherapies in second-line treatment of SCCA. The aim of this study is to evaluate the combination of atezolizumab and mDCF as first-line chemotherapy in a non-comparative multicentre randomized phase II study of advanced SCCA patients.MethodsPatients with chemo-naive advanced histologically proven SCCA, metastatic or unresectable locally advanced recurrence, and Eastern Cooperative Oncology Group-performance status (ECOG-PS) < 2 will be eligible. The primary endpoint is a 12-month PFS rate. Using one-arm non-parametric survival with unilateral alpha type I error of 5% and a statistical power of 80%, the upper critical value for the 12-month PFS rate is 47% to reject H0. Assuming 5% lost to follow-up, 99 patients will be randomized on a 2:1 basis, 66 to the experimental arm (arm A, mDCF plus atezolizumab) and 33 to the standard arm (arm B, mDCF). In both arms, 8 cycles of mDCF will be administered. In arm A, patients receive mDCF with a fixed dose of atezolizumab (800 mg every 2 weeks) and are followed up to 1 year. Secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and an extensive biomarker programme and its correlation with the treatment efficacy.DiscussionAlthough the Epitopes-HPV02 trial has changed long-lasting prognosis of patients with SCCA in advanced stage disease, more than 50% of patients will progress at 12 months. The purpose of the SCARCE trial to establish the addition of atezolizumab to mDCF as a new standard in this rare disease. Associated biomarker studies and the control arm could contribute to better understanding of the potential synergic and tumour resistance mechanisms in SCCA.Trial registrationNCT03519295.
Highlights
Modified docetaxel, cisplatin, and 5-fluorouracil regimen has become a new standard for the treatment of metastatic or unresectable locally advanced recurrent squamous cell carcinoma of the anus (SCCA) after demonstrating improved efficacy (12-month Progression-free survival (PFS) of 47%) in the Epitopes-HPV02 trial
Discussion: the Epitopes-HPV02 trial has changed long-lasting prognosis of patients with SCCA in advanced stage disease, more than 50% of patients will progress at 12 months
The purpose of the SCARCE trial to establish the addition of atezolizumab to mDCF as a new standard in this rare disease
Summary
Cisplatin, and 5-fluorouracil (mDCF) regimen has become a new standard for the treatment of metastatic or unresectable locally advanced recurrent squamous cell carcinoma of the anus (SCCA) after demonstrating improved efficacy (12-month PFS of 47%) in the Epitopes-HPV02 trial. The modified docetaxel, cisplatin, and 5fluorouracil (mDCF) combination chemotherapy regimen has demonstrated high efficacy, with good tolerance in a phase II Epitopes-HPV02 trial of 69 SCCA patients [5] and has become the first validated chemotherapy regimen in advanced SCCA. MDCF demonstrated significantly lower toxicity compared to the standard DCF (Grade III/IV toxicity rate of 53% vs 83%) while maintaining the same efficacy [5] These encouraging results were externally validated with the updated data from the Epitopes-HPV02 trial including 51 SCCA patients.
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