In a phase III trial (TrilynX) reported in the Journal of Clinical Oncology, Bourhis et al found that the addition of xevinapant (an inhibitor of apoptosis proteins inhibitor) to platinum-based chemoradiotherapy did not improve event-free survival in patients with unresected locally advanced squamous cell carcinoma of the head and neck.
Study Details
In the international double-blind trial, 730 patients were randomly assigned between September 2020 and February 2023 to receive six cycles of xevinapant at 200 mg once daily (n = 364) or placebo (n = 366) once daily on days 1 to 14 of a 21-day cycle plus chemoradiotherapy with cisplatin at 100 mg/m2 on day 2 of an every-3-week cycle (up to three cycles) and intensity-modulated RT at 70 Gy in 35 fractions of 2 Gy/day on 5 days/week. Treatment was continued for up to six cycles. The primary endpoint was event-free survival on blinded independent review committee assessment.
Key Findings
Median event-free survival was 19.4 months (95% confidence interval [CI] = 14.5 months to not estimable) in the xevinapant group vs 33.1 months (95% CI = 21.0 months to not estimable) in the control group (hazard ratio [HR] = 1.33, 95% CI = 1.05–1.67, P = .9919).
Median progression-free survival was 26.8 months (95% CI = 15.9 months to not estimable) in the xevinapant group vs 33.1 months (95% CI = 22.8 months to not estimable) in the control group (HR = 1.24, 95% CI = 0.97–1.57). Median overall survival was not reached in either group; at time of analysis, death had occurred in 106 patients in the xevinapant group vs 81 patients in the control group (HR = 1.39, 95% CI = 1.04–1.86).
Grade ≥ 3 adverse events occurred in 87.9% of the xevinapant group vs 80.3% of the control group; the most common in both groups were anemia (21.4% vs 14.3%) and neutropenia (19.5% vs 19.4%). Grade ≥ 3 pneumonia occurred in 8.0% vs 3.1% of patients. Serious adverse events occurred in 53.3% vs 36.2% of patients. Adverse events led to discontinuation of any study treatment in 38.2% vs 24.4% of patients.
The investigators concluded: “Xevinapant plus [chemoradiotherapy] did not improve [event-free survival] ([event-free survival] was shorter with xevinapant [vs] placebo) and demonstrated an unfavorable safety profile versus placebo plus [chemoradiotherapy] in patients with unresected [locally advanced squamous cell carcinoma of the head and neck].”
Jean Bourhis, MD, of Radiation Oncology Department, Bâtiment Hospitalier, CHUV, Lausanne, Switzerland, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Debiopharm International SA and Merck. For full disclosures of all study authors, visit ascopubs.org.
