Department of Oncology, University Hospital of Besançon, 3 Boulevard Alexander Flemingn, F-25030, Besançon, France.
Hôpital Nord Franche Comté, Montbéliard, France.
BMC Cancer. 2020 Apr 25;20(1):352. doi: 10.1186/s12885-020-06841-1.
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.
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.
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.
NCT03519295.
在 Epitopes-HPV02 试验中，改良多西紫杉醇、顺铂和 5-氟尿嘧啶（mDCF）方案显示出改善的疗效（47%的 12 个月无进展生存率[PFS]），成为转移性或不可切除的局部晚期复发性肛门鳞状细胞癌（SCCA）的新治疗标准。针对检查点抑制剂（CKI）程序性死亡蛋白-1（PD1）的抗体作为 SCCA 二线治疗的单一疗法已显示出疗效。本研究旨在评估在未经化疗的晚期 SCCA 患者的非比较性多中心随机 2 期研究中，阿替利珠单抗联合 mDCF 作为一线化疗的疗效。
本研究将招募组织学证实的化疗初治、转移性或不可切除的局部晚期复发性、东部肿瘤协作组体力状态（ECOG-PS）<2 的 SCCA 患者。主要终点是 12 个月 PFS 率。采用单侧单侧 alpha Ⅰ型错误为 5%且统计效能为 80%的单侧非参数生存法，12 个月 PFS 率的上临界值为 47%，以拒绝 H0。假设 5%的患者失访，将按 2:1 的比例随机分配 99 例患者，66 例分到实验组（A 组，mDCF 联合阿替利珠单抗），33 例分到标准组（B 组，mDCF）。两组均给予 8 个周期的 mDCF 治疗。在 A 组中，患者接受 mDCF 联合固定剂量的阿替利珠单抗（每 2 周 800mg），并随访 1 年。次要终点包括总生存期、PFS、缓解率、安全性、健康相关生活质量以及广泛的生物标志物计划及其与治疗疗效的相关性。
尽管 Epitopes-HPV02 试验改变了晚期 SCCA 患者的长期预后，但仍有超过 50%的患者在 12 个月时进展。SCARCE 试验的目的是将阿替利珠单抗联合 mDCF 确立为这种罕见疾病的新标准。相关的生物标志物研究和对照组有助于更好地了解 SCCA 中潜在的协同和肿瘤耐药机制。
NCT03519295。
