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 (1) , Xu-Shan Sun (2) , Yoann Pointreau (3) , Christophe Le Tourneau (4, 5) , Christian Sire (6) , Marie-Christine Kaminsky (7) , Alexandre Coutte (8, 9) , Marc Alfonsi (10) , Benôit Calderon (10) , Pierre Boisselier (11) , Laurent Martin (12) , Jessica Miroir (13) , Jean-Francois Ramee (14) , Jean-Pierre Delord (15, 16) , Florian Clatot (17, 18) , Frederic Rolland (19, 20) , Julie Villa (21) , Nicolas Magne (22) , Olgun Elicin (23) , Elisabeta Gherga (2) , France Nguyen (1) , Cédrik Lafond (3) , Guillaume Bera (6) , Valentin Calugaru (4, 5) , Lionnel Geoffrois (7) , Bruno Chauffert (8) , Lars Damstrup (24) , Philippa Crompton (24) , Abdallah Ennaji (24) , Kathrin Gollmer (24) , Heidi Nauwelaerts (24) , Jean Bourhis (25)

1 IGR - Institut Gustave Roussy
2 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
3 Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans]
4 Institut Curie [Paris]
5 Université Paris-Saclay
6 GHBS - Groupe Hospitalier Bretagne Sud
7 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
8 CHU Amiens-Picardie
9 CHIMERE - CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516
10 Institut Sainte Catherine [Avignon]
11 ICM - Institut du Cancer de Montpellier
12 CGLC - Centre de radiothérapie Guillaume le Conquérant
13 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
14 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
15 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
16 Institut Claudius Regaud
17 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
18 Département d'oncologie médicale [Rouen]
19 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
20 CRLCC René Gauducheau
21 CHU - Centre Hospitalier Universitaire [Grenoble]
22 Institut de Cancérologie Lucien Neuwirth
23 University of Bern
24 EPFL - Debiopharm International SA
25 CHUV - Centre Hospitalier Universitaire Vaudois [Lausanne]

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: Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cycle 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. 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.

Mots clés: Chemoradiotherapy; Efficacy; Locally advanced squamous cell carcinoma of the head and neck; Survival; Xevinapant

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie

Yungan Tao, Xu-Shan Sun, Yoann Pointreau, Christophe Le Tourneau, Christian Sire, et al.. 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. European Journal of Cancer, 2023, 183, pp.24-37. ⟨10.1016/j.ejca.2022.12.015⟩. ⟨hal-04002440⟩