Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
Moores Cancer Center, University of California San Diego, La Jolla, CA.
J Clin Oncol. 2020 Jul 20;38(21):2427-2437. doi: 10.1200/JCO.19.03156. Epub 2020 Jun 1.
Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.
Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS).
The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m. EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively.
Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.
帕博利珠单抗是一种人源化单克隆抗体，可阻断程序性死亡受体-1（PD-1）与其配体（PD-L1、PD-L2）之间的相互作用。尽管帕博利珠单抗已被批准用于复发性/转移性头颈部鳞状细胞癌（HNSCC），但其在局部晚期（LA）疾病管理中的作用尚未确定。我们报告了一项评估帕博利珠单抗联合顺铂为基础的放化疗治疗 LA HNSCC 患者的安全性和疗效的 Ib 期研究。
符合条件的患者包括口腔（不包括唇）、口咽、下咽或喉的 III 至 IVB 期 HNSCC（根据美国癌症联合委员会第 7 版分期系统），适合顺铂为基础、标准剂量（70Gy）放化疗。帕博利珠单抗与放化疗同期给予，每周给予顺铂，放化疗后继续给予。主要终点是放化疗不良事件（AE）和免疫相关不良事件（irAE）的发生率。根据治疗结束（EOT）影像学或放疗后 100 天的病理确认，疗效定义为完全缓解（CR）率。主要次要终点包括总生存期（OS）和无进展生存期（PFS）。
该研究于 2015 年 11 月至 2018 年 10 月期间共入组 59 例患者（HPV 阳性，n=34；HPV 阴性，n=25）。5 例（8.8%）患者因 irAE 而停止使用帕博利珠单抗，均发生在同期放化疗期间；98.3%的患者接受了完整的计划放疗剂量（70Gy），没有任何≥5 天的延迟；88.1%的患者完成了目标顺铂剂量≥200mg/m2。HPV 阳性和阴性 HNSCC 的 EOT CR 率分别为 85.3%和 78.3%。
帕博利珠单抗联合每周顺铂为基础的放化疗是安全的，不会损害 HNSCC 的根治性放疗或化疗的实施。早期疗效数据支持进一步研究该方法。
