Journal Article

Atezolizumab plus modified docetaxel-cisplatin-5-fluorouracil (mDCF) regimen versus mDCF in patients with metastatic or unresectable locally advanced recurrent anal squamous cell carcinoma: a randomized, non-comparative phase II SCARCE GERCOR trial

Kim, Stefano, El Hajbi, Farid, François, Éric, Spehner, Laurie, Baba-Hamed, Nabil, Desramé, Jérôme, Bouché, Olivier, Jary, Marine, Bidard, François-Clément, Smith, Denis, Vendrely, Véronique, Taieb, Julien, André, Thierry, Parzy, Aurélie, Jacquin, Marion, Samalin, Emmanuelle, Dahan, Laëtitia, Borg, Christophe, Buecher, Bruno, Rebucci-Peixoto, Magali, de la Fouchardière, Christelle, Vernerey, Dewi, Tougeron, David, Ghiringhelli, François

2020

Overview

Background Modified 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. Methods Patients 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. Discussion Although 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 registration NCT03519295 .

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 5-Fluorouracil / Advanced / Aged / Anal cancer / Anal carcinoma / Antibodies, Monoclonal, Humanized - administration & dosage / Antigenic determinants / Antigens / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Anus / Anus Neoplasms - drug therapy / Anus Neoplasms - pathology / Apoptosis / Atezolizumab / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer metastasis / Cancer Research / Carcinoma, Squamous Cell - drug therapy / Carcinoma, Squamous Cell - secondary / Cell death / Chemotherapy / Cisplatin / Cisplatin - administration & dosage / Clinical medicine / Clinical trials / Colorectal cancer / Comparative analysis / Deoxyribonucleic acid / DNA / Docetaxel / Docetaxel - administration & dosage / Drug therapy / Epitopes / Experimental therapeutics and drug development / Female / Fluorouracil / Fluorouracil - administration & dosage / Follow-Up Studies / Health Promotion and Disease Prevention / Human papillomavirus / Humans / Immune checkpoint / Immunotherapy / Life Sciences / Lymphatic Metastasis / Male / Medical prognosis / Medical research / Medicine/Public Health / Metastases / Metastasis / Monoclonal antibodies / Neoplasm Recurrence, Local - drug therapy / Neoplasm Recurrence, Local - pathology / Neutropenia / Oncology / Patients / PD-1 protein / Product development / Prognosis / Quality of life / Rare diseases / Squamous cell carcinoma / Study Protocol / Surgical Oncology / Survival Rate / Targeted cancer therapy / Telomerase / Tumors