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
Yungan Tao, Xu-Shan Sun, Y. Pointreau, Christophe Le Tourneau, Christian Sire, Marie‐Christine Kaminsky, Alexandre Coutté, M. Alfonsi, Benôit Calderon, Pierre Boisselier, Laurent Martin, J. Miroir, Jean‐François Ramée, Jean‐Pierre Delord, Florian Clatot, Frédéric Rolland, Julie Villa, Nicolas Magné, Olgun Eliçin, Elisabeta Gherga, F. Nguyen, Cédrik Lafond, G. Béra, Valentin Calugaru, Lionnel Geoffrois, Bruno Chauffert, Lars Damstrup, Philippa Crompton, Abdallah Ennaji, Kathrin Gollmer, Heidi Nauwelaerts, Jean Bourhis
Abstract
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 unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). METHODS: 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. placebo 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. placebo 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 demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.