HPV circulating tumor DNA as predictive biomarker of sustained response to chemotherapy in advanced anal carcinoma

Date 20 October 2018
Event ESMO 2018 Congress
Session Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Topics Anal Cancer
Translational Research
Presenter Alice Bernard-Tessier
Citation Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269
Authors A. Bernard-Tessier1, E. Jeannot1, D. Guenat2, M. Michel3, C. Proudhon3, A. Vincent-Salomon4, I. Bièche5, J. Pierga6, B. Buecher6, E. Francois7, S. Kim8, T. André9, M. Jary8, V. Vendrely10, E. Samalin11, F. El Hajbi12, N. Baba-Hamed13, A. Meurisse14, F. Bidard15, C. Borg8
  • 1Biopathology, Institut Curie, 75005 - PARIS/FR
  • 2Centre National De Référence Papillomavirus, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 3Circulating Tumor Biomarkers Laboratory, Institut Curie, 75005 - PARIS/FR
  • 4Pathology, Institut Curie, 75005 - Paris/FR
  • 5Pharmacogenomics Unit, Institut Curie, 75005 - PARIS/FR
  • 6Service D'oncologie Médicale, Institut Curie, 75248 cedex5 - Paris/FR
  • 7Oncology, Centre Anticancer Antoine Lacassagne, 6100 - Nice/FR
  • 8Medical Oncology, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 9Medical Oncology, Hôpital Saint-Antoine, 75571 - Paris/FR
  • 10Oncology Radiotherapy, Centre Hospitalier Universitaire de Bordeaux, Bordeaux/FR
  • 11Medical Oncology, ICM Regional Cancer Institute of Montpellier, 34298 - Montpellier/FR
  • 12Medical Oncology, Centre Oscar Lambret, 59020 - Lille/FR
  • 13Medical Oncology, Groupe Hospitalier Paris Saint-Joseph, 75014 - PARIS/FR
  • 14Methodology And Quality Of Life In Oncology Unit, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 15Medical Oncology, Institut Curie, 75005 - Paris/FR

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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

NCT02402842.

Legal entity responsible for the study

Institut Curie.

Funding

Fondation ARC.

Editorial Acknowledgement

Disclosure

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.