The Epitopes-HPV02 single arm phase II study (NCT02402842) demonstrated the efficacy of Docetaxel, Cisplatin and 5FU as first line chemotherapy (CT) for advanced squamous cell carcinoma of the anal canal (SCCA), with a 1-year progression-free survival rate (PFS) of 47% (Kim, Lancet Oncol 2018 in press). We previously reported the validity of HPV ctDNA detection and its prognostic value in localized SCCA (Cabel, Clin Cancer Res 2018 in press). This ancillary study reports the impact of HPV ctDNA detection in patients enrolled in the Epitopes-HPV02 trial.
Per protocol, serum samples (1 ml) were collected twice: before CT and, in non-progressive patients, at CT discontinuation which occurred after 5 months on CT. HPV16 ctDNA was quantified by ddPCR at both time points and correlated with prospectively registered patient characteristics and outcomes; for post-CT survival analyses, a landmark was set at the time of CT discontinuation.
Among 59 patients with HPV16+ advanced SCCA, 52 (88%) had ctDNA detected at baseline (sensitivity: 91.1%; 95%CI[81.1;96.2]) with a median level of 7,148 copies/ml (range: 8.3- 3,147,000). Baseline ctDNA levels were not associated with any of the patient characteristics; ctDNA level below the median at baseline was correlated with a longer PFS (HR = 2.6, 95%CI[1.1;5.9], p = 0.02). Among 38 patients who completed the 5 months CT, residual ctDNA after CT was detected in 14 patients (36.8%; 95%CI[23.4;52.7]) with a median level of 2,662 copies/ml (range: 31.5–211,950). Residual ctDNA detected at CT discontinuation was strongly associated with shorter post-CT PFS (measured from the time of CT discontinuation, median PFS: 5.4 months vs not reached; HR = 6.2, 95%CI[2.3;16.3], p < 0.001) and OS (HR = 9.6, 95%CI[2.0;46.9], p = 0.005).
In this prospective study in advanced SCCA, we observed a strong prognostic impact of HPV ctDNA before 1st line CT and, in non-progressive patients, after 6 months of DCF. With a limited cost and short turnaround, this quantitative assay is a promising tool to optimize the therapeutic management of SCCA with e.g. maintenance anti PD-1/PD-L1 therapy in ctDNA-positive patients after the completion of first line CT.
Clinical trial identification
Legal entity responsible for the study
T. André: Honoraria and advisory role: Roche, BMS, Merck & Co. E. Samalin: Honoraria: Sanofi, Bayer, Servier, Roche; Study support: Merck, Bayer; Congress support: Roche, Ipsen. All other authors have declared no conflicts of interest.