Borel Christian, Jung Alain C, Burgy Mickaël
Department of Medical Oncology, Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, France.
Laboratoire de Biologie Tumorale, Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, France.
Cancers (Basel). 2020 Sep 21;12(9):2691. doi: 10.3390/cancers12092691.
Head and neck squamous cell carcinoma (HNSCC) in the recurrent or metastatic (R/M) setting is a devastating disease with a poor prognosis. Until recently, the reference first line treatment was the EXTREME protocol, which yields a 10.1 months median survival, and almost no effective treatment are available in second line. Immune checkpoint inhibitors (ICIs) have changed the prognosis of several metastatic solid tumors. Given their inflammatory profile and high mutational burden, HNSCC is a good candidate for ICIs treatments. First, a strong pembrolizumab efficacy signal was shown in the Keynote-012 Phase Ib study. Then, the phase III Checkmate-141 study validated the efficacy of nivolumab in platinum-resistant patients. Finally, the first line conquest is acquired since the final results of the keynote-048 phase III study that demonstrated the superiority of pembrolizumab versus EXTREME in CPS ≥ 1 patients, and with the addition of platinum and 5FU in all patients. However, the first line treatment landscape is not frozen. Two studies (Checkmate-651 and Kestrel) are investigating the efficacy of the combination of antibodies raised against CTLA-4 and PD-(L)1. Results are impatiently awaited. Further progress needs the use of new immunotherapeutic agents such as monalizumab or ICOS agonist rather in combination with an anti-PD(L)1. New associations of ICIs and chemotherapeutic or targeted therapeutic agents are also actively investigated. Finally, ICIs has to be studied in the locally advanced setting where there is a chance of cure. Several trials are testing the potential synergistic combination of ICIs with radiotherapy and platinum or cetuximab, or ICIs used in a neoadjuvant setting.
复发或转移性（R/M）头颈部鳞状细胞癌（HNSCC）是一种预后很差的毁灭性疾病。直到最近，标准的一线治疗方案是EXTREME方案，其总生存期中位数为10.1个月，二线治疗几乎没有有效的治疗方法。免疫检查点抑制剂（ICI）改变了几种转移性实体瘤的预后。鉴于其炎症特征和高突变负荷，HNSCC是ICI治疗的良好候选者。首先，在Keynote-012 Ib期研究中显示了帕博利珠单抗的强大疗效信号。然后，III期Checkmate-141研究验证了纳武利尤单抗在铂耐药患者中的疗效。最后，随着III期Keynote-048研究的最终结果表明，帕博利珠单抗在CPS≥1的患者中优于EXTREME方案，并且所有患者都添加了铂和5-氟尿嘧啶（5FU），一线治疗格局得以确立。然而，一线治疗格局并非一成不变。两项研究（Checkmate-651和Kestrel）正在研究抗CTLA-4和PD-（L）1抗体联合使用的疗效。结果令人期待。进一步的进展需要使用新的免疫治疗药物，如莫纳利珠单抗或ICOS激动剂，而不是与抗PD（L）1联合使用。ICI与化疗或靶向治疗药物的新联合也在积极研究中。最后，必须在有治愈机会的局部晚期环境中研究ICI。几项试验正在测试ICI与放疗和铂或西妥昔单抗的潜在协同联合，或在新辅助治疗中使用ICI。
