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

Abstract

Aims: The addition of docetaxel to cisplatin and 5-fluorouracil (DCF) has shown promising efficacy in advanced squamous cell carcinoma of the anus (SCCA). Preliminary results of Epitopes-HPV01 study showed a high rate of long-lasting complete response to DCF. The prospective, multicenter, Epitopes-HPV02 trial then confirmed the high efficacy of the modified DCF (mDCF) regimen in terms of complete response rate and long-term survival in metastatic or non-resectable locally advanced recurrent SCCA. Here, we present updated results of the Epitopes-HPV01 and Epitopes-HPV02 studies. Patients & methods: Epitopes-HPV01 is a prospective study performed by the regional cancer network of Franche-Comté, France. Epitopes-HPV02 is a phase II study supported by two French collaborative oncological groups, performed in 25 centers. Both studies included patients with metastatic, or with unresectable local recurrent SCCA, treated with DCF regimen. Results: In Epitopes-HPV01, 51 patients were enrolled between September 2012 and January 2019, and 49 patients were included for analysis; while 69 patients were included between September 2014 and December 2016 in Epitopes-HPV02, and 66 patients for analysis. Pooled analysis of 115 patients showed a median progression-free survival of 12.2 months [95% confidence interval (CI) 10.6–16.1] [11.0 months (9.3–16.0) in -HPV02, and 15.6 months (11.2–34.5) in -HPV01, ( p = 0.06)]. The median overall survival was 39.2 months (26.0–109.1) [36.3 in -HPV02 (25.2–NR), and 61.1 months (21.4–120.0) in -HPV01 ( p = 0.62)]. Objective response rate was 87.7% (90.9% in -HPV02 and 83.3% in -HPV01) with 40.3% of complete response (45.5% in -HPV02 and 33.3% in -HPV01). No differences were observed between standard DCF ( n = 54) and mDCF ( n = 58) in terms of OS ( p = 0.57) and PFS ( p = 0.99). 5-years PFS and OS rates were 24.5% and 44.4%, respectively, in the whole population. No treatment-related death was observed. Conclusion: Updated results of Epitopes-HPV01 and 02 studies, as well as the pooled analysis, confirm mDCF as a standard treatment in patients with advanced SCCA.

Present and Future Research on Anal Squamous Cell Carcinoma

“…In Epitopes-HPV02 study, a subgroup of 16 patients with synchronous metastases previously untreated, all patients presented an objective response after DCF with 56% of complete response of all involved sites including primary tumor [10]. The pooled analysis of Epitope-HPV01 and Epitopes-HPV02 studies confirmed these data [16]. None of the 29 patients with synchronous metastases presented a disease-progression at first evaluation during DCF administration, and the ORR was reached in 26 (89.7%) patients, including 16 (55.2%) patients with a complete response.…”

“…In addition, in the whole Epitopes-HPV population of 115 patients treated with DCF, 25% of patients were still alive and disease-free at 5 years. Along with the high complete response rate, these findings suggest the potential use of DCF in neoadjuvant/adjuvant setting [16]. Anti-PD1/L1 antibodies are also potential candidates since long-lasting complete responses have been seen in chemorefractory patients in advanced SCCA [51].…”

“…Modified DCF is the most effective (complete response rate, 40.3%) with the best safety profile (grade 3/4 toxicity rate, 53%) treatment among combined chemotherapy regimens in first line and became standard in advanced SCCA [10,16]. Interestingly, the conversion from positive to negative HPV ctDNA on liquid biopsy, which is highly predictive of better prognosis, was achieved in 61.1% (22/36) of patients with DCF in the Epitopes-HPV02 trial, compared to 17.9% (5/28) of patients with doublet chemotherapy in InterAACT trial [11,16,23]. In consequence, CP regimen should be considered as an option in patients with a contraindication to 5FU or cisplatin (e.g., impaired renal function and active cardiovascular disease) [16,80].…”

“…mDCF became the first prospectively validated standard regimen in metastatic SCCA [14,15]. Recently, a pooled analysis of updated data of 115 patients in Epitopes-HPV01 and 02 trials demonstrated a long-lasting complete response in 25% of patients at 5 years, with an overall survival rate of 44% after DCF [16]. Second, the InterAACT "pick the winner" randomized phase II trial evaluated two doublet regimens: carboplatin plus paclitaxel (CP), and cisplatin plus 5-fluorouracil (CP).…”

Metastatic or Locally Recurrent Anal Squamous Cell Carcinoma (SCAC): Current Clinical Trial Landscape and Novel Approaches

“…An updated analysis with longer follow-up time pooled the results of the Epitopes-HPV01 and the Epitopes-HPV02 studies together. 19 A pooled analysis (n = 115) showed a median PFS of 12 months (95% CI, 10.6 to 16.0) and median OS of 50.2 months (95% CI, 26.0 to 120.0). The ORR was 87.7%, comprised of 40.7% CRs.…”