Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study)

Abstract

BackgroundThe squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months.We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses.Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients.MethodsThis multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon’s optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy.DiscussionSince the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA.Trial registration NCT02402842, EudraCT: 2014–001789-81.

Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma

“…In Epitopes-HPV02, 69 patients were enrolled between 17 September 2014 and 7 December 2016 and 66 patients were included for analysis (Figure 1). 13 We locked the database for Epitopes-HPV02 for updated analysis on 20 July 2020 with a median follow up of 40.1 months (95% CI 39.4-40.7). At data lock, 13 (19.7%) patients were still alive and free of progression.…”

Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial

“…Epitopes-HPV02 (NCT02402842) was a phase II multicenter prospective single-arm trial, in which the primary objective was to assess the efficacy of DCF regimen as first-line palliative chemotherapy for patients with SCCA. Detailed eligibility criteria and treatments have been reported elsewhere (16). Main eligibility criteria were: patients with unresectable locally advanced recurrent or metastatic SCCA; performance status: 0 or 1; no prior chemotherapy for metastatic or recurrent SCCA; signed informed consent.…”

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

“…We have previously shown promising results with the addition of docetaxel to DCF in our Epitopes-HPV01 cohort study [9]. Four patients (out of eight) presented a long-lasting remission, providing a clinical rational for a prospective multicentre phase II Epitopes-HPV02 trial of 66 SCCA evaluable patients [25]. The trial confirmed the efficacy of this combination and settled the mDCF regimen as a new standard first-line chemotherapy [5].…”