LBA33 - 5-year overall survival (OS) in patients (pts) with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) treated with xevinapant + chemoradiotherapy (CRT) vs placebo + CRT in a randomized, phase II study

Background

In a double-blind, randomized, phase 2 study of pts with unresected LA SCCHN (NCT02022098), xevinapant + standard-of-care (SOC) CRT significantly improved locoregional control at 18 months after end of CRT (primary endpoint) and 3-year progression-free survival vs placebo + CRT, without increasing toxicity. Here we report updated data on duration of response (DoR) after 3 years and OS after 5 years.

Methods

Pts with unresected LA SCCHN, stratified by node involvement, primary tumor site, and HPV-16 status in pts with oropharyngeal tumors, were randomized (1:1) to receive xevinapant 200 mg once daily (days 1-14 of a 3-week cycle every 3 weeks [Q3W]) for 3 cycles + CRT (cisplatin 100 mg/m² on day 2 Q3W for 3 cycles; intensity-modulated radiotherapy 70 Gy [2 Gy/day, 5 days/week for 7 weeks]) or placebo + CRT for 3 cycles.

Results

Between January 2016 and April 2017, 96 pts were randomized and followed up for disease progression until July 2020; survival data were collected until April 2022 (5 years after last patient randomized). The risk of death or disease progression after initial response was reduced by 79% in the xevinapant vs placebo arm (DoR; adjusted HR, 0.21; 95% CI, 0.08-0.54, p=0.0011). For long-term OS, median follow-up was 60.1 months (range, 7.1-70.5 months) in the xevinapant arm and 39.2 months (range, 4.8-71.2 months) in the placebo arm. The risk of death was more than halved in the xevinapant vs placebo arm (adjusted HR, 0.47 [95% CI, 0.27-0.84]; p=0.0101). OS was prolonged with xevinapant + CRT vs placebo + CRT; median OS was not reached (95% CI, 40.3 months-not evaluable) vs 36.1 months (95% CI, 21.8-46.7 months), and the probability of survival 5 years after randomization was 53% (95% CI, 37-66%) vs 28% (95% CI, 15-42%), respectively.

Conclusions

Adding xevinapant to SOC CRT improved 5-year OS in pts with unresected LA SCCHN vs placebo + CRT, with a marked improvement in 3-year DoR also observed. A pivotal phase 3 study of xevinapant + CRT in pts with unresected LA SCCHN (Trilynx; NCT04459715) is ongoing.

Clinical trial identification

NCT02022098.

Editorial acknowledgement

Medical writing support was provided by Sophie Saunders of ClinicalThinking, which was funded by Merck in accordance with Good Publication Practice guidelines. (http://www.ismpp.org/gpp3).

Legal entity responsible for the study

Debiopharm.

Funding

Debiopharm.

Disclosure

J. Bourhis: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Debiopharm, Merck, MSD, Nanobiotix, Roche. C. Le Tourneau: Financial Interests, Personal and Institutional, Advisory Role: MSD, BMS, AstraZeneca, Nanobiotix, Celgene, Seattle Genetics, MaxiVac, Roche, PCI BioTech, Onxeo, ALX Oncology. Y. Pointreau: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Role: Merck. J. Delord: Financial Interests, Institutional, Advisory Board: Roche, MSD, BMS, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Merck Serono; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Amgen, Genentech, Transgene, MSD. F. Clatot: Financial Interests, Institutional, Research Grant: Roche diagnostics, AstraZeneca; Financial Interests, Personal, Advisory Role: Merck, MSD, BMS, Roche, Eli Lilly, AstraZeneca. O. Elicin: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, MSD. L. Damstrup: Financial Interests, Personal, Full or part-time Employment: Debiopharm International SA. K. Gollmer: Financial Interests, Personal, Full or part-time Employment: Debiopharm International SA. P. Crompton: Financial Interests, Personal, Full or part-time Employment: Debiopharm International SA. Y. Tao: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Other, Travel: MSD, Merck. All other authors have declared no conflicts of interest.