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.

Abstract

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.

• Authors: Stefano Kim, Bruno Buecher, Thierry André, Marine Jary, François-Clément Bidard, François Ghiringhelli, Éric François, Julien Taieb, Denis Smith, Christelle de la Fouchardière, Jérôme Desramé, Emmanuelle Samalin, Aurélie Parzy, Nabil Baba-Hamed, Olivier Bouché, David Tougeron, Laëtitia Dahan, Farid El Hajbi, Marion Jacquin, Magali Rebucci-Peixoto, Laurie Spehner, Véronique Vendrely, Dewi Vernerey, Christophe Borg
• Journal: BMC cancer (BMC Cancer) Vol. 20 Issue 1 Pg. 352 (Apr 25 2020) ISSN: 1471-2407 [Electronic] England
• PMID: 32334548 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal, Humanized
• Docetaxel
• atezolizumab
• Cisplatin
• Fluorouracil

Topics

• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Anus Neoplasms (drug therapy, pathology)
• Carcinoma, Squamous Cell (drug therapy, secondary)
• Cisplatin (administration & dosage)
• Docetaxel (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Humans
• Lymphatic Metastasis
• Male
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Prognosis
• Survival Rate