Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial

Susanne Wiegand; Gunnar Wichmann; Jeannette Vogt; Kathrin Vogel; Annegret Franke; Thomas Kuhnt; Florian Lordick; Anne-Marie Scheuble; Peter Hambsch; Peter Brossart; Franz Georg Bauernfeind; Holger Kaftan; Georg Maschmeyer; Matthias Paland; Marc Münter; Victor Lewitzki; Nicole Rotter; Carmen Stromberger; Marcus Beck; Steffen Dommerich; Thomas Christoph Gauler; Gunnar Hapke; Orlando Guntinas-Lichius; Ursula Schröder; Martin Görner; Matthias G Hautmann; Felix Steger; Bálint Tamaskovics; Anett Schmiedeknecht; Andreas Dietz

doi:10.3389/fonc.2023.1128176

Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial

Front Oncol. 2023 Mar 21:13:1128176. doi: 10.3389/fonc.2023.1128176. eCollection 2023.

Authors

Susanne Wiegand¹, Gunnar Wichmann¹, Jeannette Vogt¹, Kathrin Vogel¹, Annegret Franke², Thomas Kuhnt³, Florian Lordick⁴, Anne-Marie Scheuble⁴, Peter Hambsch³, Peter Brossart⁵, Franz Georg Bauernfeind⁵, Holger Kaftan⁶, Georg Maschmeyer⁷, Matthias Paland⁷, Marc Münter⁸, Victor Lewitzki⁹, Nicole Rotter¹⁰, Carmen Stromberger^{11

12}, Marcus Beck¹¹, Steffen Dommerich¹³, Thomas Christoph Gauler¹⁴, Gunnar Hapke¹⁵, Orlando Guntinas-Lichius¹⁶, Ursula Schröder¹⁷, Martin Görner¹⁸, Matthias G Hautmann¹⁹, Felix Steger¹⁹, Bálint Tamaskovics²⁰, Anett Schmiedeknecht², Andreas Dietz¹

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Leipzig University Medical Center, Leipzig, Germany.
² Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany.
³ Department of Radiation Oncology, University Hospital Leipzig, Leipzig, Germany.
⁴ University Cancer Center Leipzig, Leipzig University Medical Center, Leipzig, Germany.
⁵ Department of Oncology, Hematology, Immuno-Oncology, Rheumatology and Clinical Immunology, University Hospital Bonn, Bonn, Germany.
⁶ Department of Otorhinolaryngology, Helios-Klinikum Erfurt, Erfurt, Germany.
⁷ Department of Haematology, Oncology, and Palliative Care, Ernst Von Bergmann Clinic, Potsdam, Germany.
⁸ Institute of Radiotherapy, Klinikum Stuttgart, Stuttgart, Germany.
⁹ Department of Radiation Oncology, University of Würzburg, Würzburg, Germany.
¹⁰ Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Mannheim, Mannheim, Germany.
¹¹ Department of Radiation Oncology, Charité, Berlin, Germany.
¹² Vivantes Klinikum Neukölln, Department of Radiooncology and Radiotherapy, Berlin, Germany.
¹³ Department of Otolaryngology, Charité, Berlin, Germany.
¹⁴ Department of Radiotherapy, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
¹⁵ Department of Hematology and Oncology, Marienkrankenhaus Hamburg, Hamburg, Germany.
¹⁶ Department of Otorhinolaryngology, Jena University Hospital, Jena, Germany.
¹⁷ Department of Otorhinolaryngology, University of Lübeck, Lübeck, Germany.
¹⁸ Department of Hematology, Oncology and Palliative Medicine, Klinikum Bielefeld Mitte, Bielefeld, Germany.
¹⁹ Department for Radiotherapy, University Hospital Regensburg, Regensburg, Germany.
²⁰ Department of Radiation Oncology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.

Abstract

Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery will be eligible. Two hun-dred forty patients will be randomly assigned (1:1) to either standard aRCT with cisplatin (standard arm) or aRCT with cisplatin + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months) (interventional arm). Endpoints are event-free and overall survival. Recruitment started in August 2018 and is ongoing.

Keywords: PD-1:PD-L1 axis; head neck cancer; immune checkpoint blockade; immunotherapy; locoregional disease; pembrolizumab; randomized controlled phase IIB clinical trial; upfront surgery.

Copyright © 2023 Wiegand, Wichmann, Vogt, Vogel, Franke, Kuhnt, Lordick, Scheuble, Hambsch, Brossart, Bauernfeind, Kaftan, Maschmeyer, Paland, Münter, Lewitzki, Rotter, Stromberger, Beck, Dommerich, Gauler, Hapke, Guntinas-Lichius, Schröder, Görner, Hautmann, Steger, Tamaskovics, Schmiedeknecht and Dietz.

Grants and funding

This trial is funded by MSD Sharp & Dohme GmbH. The funding body has no influence on the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. This publication was funded by the Open Access Publishing Fund of Leipzig University, supported by the German Research Foundation within the program Open Access Publication Funding.