Pembrolizumab in the first-line treatment of advanced head and neck cancer

Recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis and has limited therapeutic options. PD-1/PD-L1 axis blockade was initially shown to improve outcomes in platinum-refractory HNSCC. More recently, pembrolizumab monotherapy or pembrolizumab combined with chemotherapy resulted in better overall survival than platinum, 5-fluorouracil, and cetuximab (EXTREME regimen) as first-line therapy for R/M HNSCC, establishing a new standard-of-care therapy for this disease. We review pembrolizumab in the first-line treatment of R/M HNSCC and summarize the impact of PD-L1 expression, tumor and symptom burden, and patient’s performance status on treatment decisions. Future perspectives are summarized. The standard-of-care first-line therapy for R/M HNSCC is pembrolizumab monotherapy for patients with a PD-L1 combined positive score (CPS)≥1 or pembrolizumab combined with platinum and 5-fluorouracil for patients with any PD-L1 status. Addition of chemotherapy to pembrolizumab increases the response rate but also toxicity and is preferred for patients with good performance status and significant tumor and symptom burden. For patients with a PD-L1 CPS <1, the EXTREME regimen should be considered. New strategies combining pembrolizumab with targeted therapies and immune checkpoints inhibitors are being explored to synergize or overcome resistance to anti-PD-1.

复发或转移性（recurrent or metastatic, R/M）头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）预后极差，且治疗选择十分有限。PD-1/PD-L1轴阻断治疗最初被证实可改善铂类难治性HNSCC患者的预后。近年来，帕博利珠单抗（pembrolizumab）单药或帕博利珠单抗联合化疗用于R/M HNSCC一线治疗时，相较铂类、5-氟尿嘧啶及西妥昔单抗组成的EXTREME方案，可带来更优的总生存期，由此确立了该疾病新的一线标准治疗方案。本文综述了帕博利珠单抗在R/M HNSCC一线治疗中的应用，并总结了PD-L1表达水平、肿瘤与症状负荷以及患者体能状态对治疗决策的影响，同时概述了未来的研究展望。R/M HNSCC的一线标准治疗方案为：对于PD-L1联合阳性评分（combined positive score, CPS）≥1的患者，采用帕博利珠单抗单药治疗；对于任意PD-L1表达状态的患者，则采用帕博利珠单抗联合铂类与5-氟尿嘧啶的治疗方案。在帕博利珠单抗基础上加用化疗可提高客观缓解率，但同时也会增加毒性反应，因此更适合体能状态良好且肿瘤与症状负荷较高的患者。对于PD-L1 CPS＜1的患者，则应考虑采用EXTREME方案。目前正在探索将帕博利珠单抗与靶向治疗、免疫检查点抑制剂联合的新型治疗策略，以期实现协同增效或克服抗PD-1治疗耐药性。