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

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. 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. 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. 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.