ESTRO 2025 - Abstract Book

S1130

Clinical – Head & neck

ESTRO 2025

4361

Proffered Paper A prospective randomized multicenter trial of Nimorazole as hypoxic modifier of accelerated chemo radiotherapy for locally advanced HPV-neg HNSCC. Vincent Gregoire 1 , Yun Gan Tao 2 , Johannes Kaanders 3 , Jean-Pascal Machiels 4 , Noémie Vulquin 5 , Sandra Nuyts 6 , Jan Alsner 7 , Jens Overgaard 7 1 Radiation Oncology, Centre Léon Bérard, Lyon, France. 2 Radiation Oncology, Institut Gustave-Roussy, Villejuif, France. 3 Radiation Oncology, RadboudUMC, Nijmegen, Netherlands. 4 Medical Oncology, Cliniques Universitaires St Luc, Brussels, Belgium. 5 Oncologue-Radiothérapeute, Centre Georges François LECLERC, Dijon, France. 6 Radiation Oncology, UZ Gasthuisberg, Leuven, Belgium. 7 Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark Purpose/Objective: The study was initiated to demonstrate/confirm the benefit of the hypoxic radiosensitizer nimorazole (NIM) with accelerated concomitant chemo-radiotherapy, and the predictive value of a hypoxic 15-gene signature. Material/Methods: Patients with stage III-IV laryngeal, hypopharyngeal or HPV-negative oropharyngeal SCC were randomized between NIM and placebo, given concomitantly with chemo-radiotherapy. Pts were stratified using a 15-hypoxic-gene signature. Accelerated radiotherapy was delivered using IMRT (70 Gy in 6 weeks). Total Cisplatin dose was 200 mg/m2 either weekly (40 mg/m2 on week 1 to 5) or 3-weekly (100 mg/m2 on weeks 1 & 4). NIM or placebo were delivered orally with a daily dose of 1.2 mg/m2. The primary endpoint was 3-year locoregional failure. Secondary endpoints included disease specific survival (DSS), overall survival (OS), and acute and late morbidity. A final institutional revision of the tumor and survival data was recently performed. Results: Between Aug 2014 and Dec 2017 where the trial was prematurely closed due to low recruitment, economic issues and concern about nephrotoxicity in the 3-weekly regimen, a total of 194 patients (92 oroph, 59 hypoph and 43 lar) were randomized out of 640 planned. Most patients had T3-T4 (76%) and N2-3 (66%) tumors. Weekly Cisplatin was given to 122 patients (60 NIM, 62 placebo), and 72 patients received 3-weekly Cisplatin (37 NIM, 35 placebo). Thirty-three % of tumors were hypoxic gene positive. At 3-years, the univariate cumulative incidence of locoregional failure were 18% for NIM and 30% for placebo, (HR 0.63, 0.35-1.16), with corresponding values for DSS (HR 0.96, 0.51-1.82), and OS (HR 1.12, 0,69-1.80) (Figure 1).