Xevinapant or Placebo Plus Platinum-Based Chemoradiotherapy in Unresected Locally Advanced Squamous Cell Carcinoma of the Head and Neck (TrilynX): A Randomized, Phase III Study.

Methods

Patients with unresected LA SCCHN (oropharynx [p16-negative only], hypopharynx, or larynx) were randomly assigned 1:1 to six cycles of oral xevinapant 200 mg/day or matched placebo (once daily on Days 1-14 of a 21-day cycle) plus CRT for the first three cycles (cisplatin [100 mg/m2 once on Day 2 of every cycle] plus intensity-modulated radiotherapy [70 Gy; 35 fractions of 2 Gy/day, 5 days/week]).

无法手术切除的局部晚期头颈部鳞状细胞癌（LA SCCHN）患者（仅限于 p16 阴性的口咽癌、下咽癌或喉癌）被随机分配，按照 1:1 的比例接受六周期的口服 xevinapant 200 mg/天或匹配的安慰剂（在 21 天周期的第 1-14 天每天一次）加上前三周期的同步放化疗（顺铂 [每周期第 2 天 100 mg/m2 单次给药] 加强度调制放疗 [70 Gy; 每日 2 Gy 分 35 次，每周 5 天]）。

The primary end point was event-free survival (EFS) assessed by the blinded independent review committee.

主要终点是由盲法独立评审委员会评估的无事件生存（EFS）

Progression-free survival, overall survival(OS), and safety were secondary end points.

无进展生存、总生存（OS）和安全性是次要终点。

Results

Between September 20, 2020, and February 27, 2023, 730 patients were randomly assigned to xevinapant plus CRT (n = 364) or placebo plus CRT (n = 366).

2020年9月20日至2023年2月27日期间，730名患者被随机分配接受xevinapant联合放化疗(n = 364)或安慰剂联合放化疗(n = 366)。

The median (95% CI) EFS was 19.4 months (14.5 to not estimable) with xevinapant and 33.1 months (21.0 to not estimable) with placebo (hazard ratio[HR], 1.33 [95% CI, 1.05 to 1.67]; P = .9919).

使用xevinapant的中位无进展生存期（95%置信区间）为19.4个月（14.5至不可估计），而使用安慰剂的为33.1个月（21.0至不可估计）（风险比[HR]，1.33 [95%置信区间，1.05至1.67]；P = .9919）。

OS was worse in the xevinapant arm (HR, 1.39 [95% CI, 1.04 to 1.86]).

xevinapant组的总生存期较差（HR，1.39 [95% 置信区间，1.04至1.86]）。

Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 320 (87.9%; xevinapant) and 286 (80.3%; placebo) patients; anemia (78 [21.4%] v 51 [14.3%]) and neutropenia (71 [19.5%] v 69 [19.4%]) were the most common.

在320名（87.9%；xevinapant）和286名（80.3%；安慰剂）患者中发生了3级或更高级别的治疗后不良事件（TEAEs）；贫血（78 [21.4%] 对比 51 [14.3%]）和中性粒细胞减少症（71 [19.5%] 对比 69 [19.4%]）是最常见的。

Serious TEAEs occurred in 194 (53.3%; xevinapant) and 129 (36.2%; placebo) patients.

严重不良事件在194名(53.3%；xevinapant组)和129名(36.2%；安慰剂组)患者中发生。

TEAEs leading to death occurred in 22 (6.0%; xevinapant) and 13 (3.7%; placebo) patients.

导致死亡的不良事件在22名(6.0%；xevinapant组)和13名(3.7%；安慰剂组)患者中发生。

Conclusions

Xevinapant plus CRT did not improve EFS (EFS was shorter with xevinapant v placebo) and demonstrated an unfavorable safety profile versus placebo plus CRT in patients with unresected LA SCCHN.

在未切除的局部晚期头颈部鳞状细胞癌患者中，Xevinapant联合放化疗并未改善无进展生存期（EFS），与安慰剂联合放化疗相比，EFS更短，并显示出与安慰剂联合放化疗相比不利的安全性特征。