美国布列根和妇女医院Ravindra Uppaluri团队研究了新辅助和辅助派姆单抗治疗局部晚期头颈癌的疗效与安全性。该项研究成果发表在2025年6月18日出版的《新英格兰医学杂志》上。

对于局部晚期头颈部鳞状细胞癌（HNSCC）患者，围手术期在手术和辅助治疗的标准护理中添加派姆单抗的益处尚不清楚。

在这项3期开放标签试验中，研究组以1:1的比例随机分配局部晚期HNSCC患者，接受2个周期的新辅助派姆单抗和15个周期的辅助派姆单抗（剂量均为每3周200 mg），此外还有标准治疗（派姆单抗组）或单独标准治疗（对照组）。标准治疗是手术和辅助放疗，伴或不伴顺铂。主要终点是无事件生存期，依次评估肿瘤表达程序性死亡配体1 （PD-L1）且综合阳性评分（CPS）为10或10以上的参与者（CPS-10人群），肿瘤表达PD-L1且CPS为1或1以上的参与者（CPS-1人群）以及所有参与者。CPS越高，表明表达PD-L1的细胞比例越高。

共有363名参与者（234名CPS≥10，347名CPS≥1）被分配到派姆单抗组，351名参与者（231名CPS≥10，335名CPS≥1）被分配到对照组。每组中大约88%的参与者完成了手术。在第一次中期分析中，中位随访时间为38.3个月。36个月时，派姆单抗组无事件生存率为59.8%，对照组为45.9% (进展、复发或死亡的风险比为0.66；95%置信区间为0.49 ~ 0.88；双侧P=0.004)；分别为58.2%和44.9% (风险比0.70；95% CI, 0.55 ~ 0.89；双侧P=0.003)，在CPS-1人群中；分别为57.6%和46.4%(风险比0.73；95% CI, 0.58 ~ 0.92；双侧P=0.008)。在派姆单抗组和对照组中，分别有44.6%和42.9%的参与者发生了3级或更高级别的治疗相关不良事件，包括1.1%和0.3%的死亡。在派姆单抗组中，10.0%的参与者发生了3级或更高级别的潜在免疫介导不良事件。

研究结果表明，在标准治疗中加入新辅助和辅助派姆单抗可显著提高局部晚期HNSCC患者的无事件生存率。新辅助派姆单抗不影响手术完成的可能性。没有发现新的安全信号。

附：英文原文

Title: Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer

Author: Ravindra Uppaluri, Robert I. Haddad, Yungan Tao, Christophe Le Tourneau, Nancy Y. Lee, William Westra, Rebecca Chernock, Makoto Tahara, Kevin J. Harrington, Arkadiy L. Klochikhin, Irene Braa, Gustavo Vasconcelos Alves, Brett G. M. Hughes, Marc Oliva, Iane Pinto Figueiredo Lima, Tsutomu Ueda, Tomasz Rutkowski, Ursula Schroeder, Paul-Stefan Mauz, Thorsten Fuereder, Simon Laban, Nobuhiko Oridate, Aron Popovtzer, Nicolas Mach, Yevhen Korobko, Diogo Alpuim Costa, Anupama Hooda-Nehra, Cristina P. Rodriguez, R. Bryan Bell, Cole Manschot, Kimberly Benjamin, Burak Gumuscu, Douglas Adkins

Issue&Volume: 2025-06-18

Abstract:

BACKGROUND

The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear.

METHODS

In this phase 3, open-label trial, we randomly assigned participants with locally advanced HNSCC in a 1:1 ratio to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group). Standard care was surgery and adjuvant radiotherapy with or without concomitant cisplatin. The primary end point was event-free survival, sequentially assessed in participants whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of 10 or more (CPS-10 population), participants whose tumors expressed PD-L1 with a CPS of 1 or more (CPS-1 population), and all the participants. A higher CPS indicates a higher proportion of cells that express PD-L1.

RESULTS

A total of 363 participants (234 with a CPS of ≥10 and 347 with a CPS of ≥1) were assigned to the pembrolizumab group and 351 (231 with a CPS of ≥10 and 335 with a CPS of ≥1) to the control group. Surgery was completed in approximately 88% of the participants in each group. At the first interim analysis, the median follow-up was 38.3 months. Event-free survival at 36 months was 59.8% in the pembrolizumab group and 45.9% in the control group (hazard ratio for progression, recurrence, or death, 0.66; 95% confidence interval [CI], 0.49 to 0.88; two-sided P=0.004) in the CPS-10 population; 58.2% and 44.9%, respectively (hazard ratio, 0.70; 95% CI, 0.55 to 0.89; two-sided P=0.003), in the CPS-1 population; and 57.6% and 46.4%, respectively (hazard ratio, 0.73; 95% CI, 0.58 to 0.92; two-sided P=0.008), in the total population. Grade 3 or higher treatment-related adverse events occurred in 44.6% of the participants in the pembrolizumab group and in 42.9% of those in the control group, including death in 1.1% and 0.3%, respectively. Potentially immune-mediated adverse events of grade 3 or higher occurred in 10.0% of the participants in the pembrolizumab group.

CONCLUSIONS

The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced HNSCC. Neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. No new safety signals were identified.

DOI: NJ202506180000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2415434