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, Stéfano; Bruno, Benedetto; Thewis, André; Jary, Marine; Bidard, François‐Clément; Ghiringhelli, François; François, Ετιεννε; Taı̈eb, Julien; Smith, Denis; Fouchardière, Christelle De La; Desrame, Jérôme; Samalin, Emmanuelle; Parzy, Aurélie; Baba-Hamed, Nabil; Bouché, Olivier; Tougeron, David; Dahan, Laétitia; Hajbi, Farid El; Jacquin, Marion; Rebucci-Peixoto, Magali; Spehner, Laurie; Vendrely, V.; Vernerey, Déwi; Borg, Christophe

doi:10.1186/s12885-020-06841-1

Cited by 24 publications

(19 citation statements)

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“…[17][18][19] To date, a 10 journals.sagepub.com/home/tam randomized phase II SCARCE trial is already ongoing to evaluate the interest of mDCF regimen in association with an anti-PD-L1 antibody. 20 In summary, DCF is so far the best evidencebased chemotherapy regimen in advanced SCCA. Updated results of Epitopes-HPV01 and 02 study, as well as its pooled analysis, confirm mDCF as the regimen of choice in patients with advanced SCCA.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…The ability of DCF to deplete MDSC in some patients while generating hTERT restricted TH1 immune response established the rational to combine this chemotherapy with PD-1 neutralization by an inhibitor of PD-L1 in HPV-driven cancers. Such enticing approach is currently under investigation (A Study of mDCF in Combination or Not With Atezolizumab in Advanced Squamous Cell Anal Carcinoma (SCARCE), NCT03519295) [30].…”

Section: Discussionmentioning

confidence: 99%

Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials

Spehner

Kim

Vienot

et al. 2020

IJMS

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Docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy regimen is highly effective in advanced anal squamous cell carcinoma (SCCA), as demonstrated by the Epitopes-HPV02 study results. Here, we analyzed the impact of DCF regimen and the prognostic value of adaptive immune responses and immunosuppressive cells in SCCA patients included in two prospective studies (Epitopes-HPV01 and HPV02). The presence of T-cell responses against Human papillomavirus (HPV)16-E6/E7 and anti-telomerase (hTERT)-antigens was measured by IFNᵧ-ELISpot. Here, we showed that HPV-adaptive immune responses are increased in SCCA patients. SCCA patients also displayed enhanced circulating TH1 T-cells restricted by hTERT. Exposition to DCF increased hTERT immunity but not HPV or common viruses immune responses. Notably, the correlation of hTERT immune responses with SCCA patients’ clinical outcomes highlights that hTERT is a relevant antigen in this HPV-related disease. The influence of peripheral immunosuppressive cells was investigated by flow cytometry. While both regulatory T-cells and monocytic-myeloid-derived suppressive cells (M-MDSC) accumulated in the peripheral blood of SCCA patients, only high levels of M-MDSC were negatively correlated with hTERT adaptive immune responses and predicted poor prognosis. Altogether, our results reveal that hTERT is a relevant antigen in HPV-driven SCCA disease and that M-MDSC levels influence TH1-adaptive immune responses and patients’ survival.

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“…Moreover, immune biomarker data of Epitopes-HPV01 and -HPV02 trials showed that DCF is a good backbone chemotherapy to combine with anti-PD1/L1 since it increases antitumor human telomerase (hTert) immunity and decreases MDSC, two major factors significantly correlated with prognosis [10,24]. The association of DCF and an anti-PD1/L1 is feasible, with no particular safety signal in SCARCE trial in the metastatic setting, which evaluated DCF with or without atezolizumab [21]. The phase II INTERACT-ION is now ongoing to evaluate the efficacy and safety of DCF with ezabenlimab, an anti-PD1 antibody, as neoadjuvant treatment in stage III SCCA patients treated with CRT (NCT04719988).…”

Section: Locally Advanced Disease: Time To Shift the Paradigm?mentioning

confidence: 99%

“…To date, three randomized clinical trials are ongoing to evaluate the efficacy of a taxane-based chemotherapy with an anti-PD1/L1. The SCARCE phase II trial with mDCF+/−atezolizumab has finished its recruitment, and the final results are pending [21]. Moreover, POD1UM-303 double-blinded phase III trial with CP in combination with retifanlimab or placebo is ongoing (NCT04472429), as well as an NCI open-label phase III trial with CP+/−nivolumab (NCT04444921).…”

Section: Advanced Disease: Time For Immunotherapy-based Combinationsmentioning

confidence: 99%

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Present and Future Research on Anal Squamous Cell Carcinoma

Spehner

Boustani

Cabel

et al. 2021

Cancers

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Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination clinical trials with an anti-PD1/L1 are ongoing in localized and advanced stages, in association with radiotherapy, chemotherapy, tumor vaccines, anti-CTLA4, anti-EGFR, or antiangiogenic molecules. Moreover, a new biomarker with high sensitivity and specificity such as HPV circulating tumor DNA (HPV ctDNA) by liquid biopsy, is improving not only the prognostic measurement but also the treatment strategy guidance for this disease. Finally, better understanding of potential targets is reshaping the present and future clinical research in this unique, HPV genotype-16-related disease in the great majority of patients.

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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

Cited by 24 publications

References 25 publications

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

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

Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials

Present and Future Research on Anal Squamous Cell Carcinoma

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