Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial

Introduction: We report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unre-sected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).Methods: Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cy-cle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/ F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed.Results: The risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. pla-cebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19-1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17-0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27-0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. pla-cebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8-46.7). Incidence of late-onset grade >3 toxicities was similar across arms.Conclusions: In this randomised phase 2 study of 96 patients, xevinapant plus CRT demon-strated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study compared the long-term efficacy and overall survival of xevinapant plus standard chemoradiotherapy with placebo plus chemoradiotherapy in patients with unresected locally advanced squamous cell carcinoma of the head and neck. The results showed that xevinapant plus CRT significantly reduced the risk of locoregional failure, death or disease progression, and prolonged overall survival in patients.