Dogan V, Rieckmann T, Münscher A, Busch C-J
Department of Otorhinolaryngology, Head and Neck Surgery and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Clin Otolaryngol. 2018 Feb;43(1):13-21. doi: 10.1111/coa.12895. Epub 2017 May 29.
Recently, enormous progress in cancer therapy has been achieved by the use of immune checkpoint inhibitors. Activating the body's own immune system has added a novel and powerful therapeutic option for the treatment of melanoma and lung cancer. Furthermore, the potential use of immunotherapy is being extensively explored also in other malignancies.
This review summarises current clinical studies using immune checkpoint modulators for the treatment of head and neck cancer (HNSCC).
Systematic review.
A PubMed search from 2010 onwards was performed for the use of immune checkpoint inhibitors in clinical trials of HNSCC. An equivalent search was performed at clinicaltrials.gov. Additionally, the abstracts from the annual meetings of the ASCO, ESMO and AACR were screened.
A total of 45 relevant studies using immune checkpoint inhibitors in HNSCC were identified. In the majority of these studies, antagonistic antibodies targeting the immune checkpoint receptors PD-1 are used either solely or combined, mostly with other immunomodulatory antibodies, such as inhibitors of CTLA-4. Most studies are still recruiting patients (26/45). In the primary setting, we identified 16 studies using checkpoint inhibition as neoadjuvant/adjuvant modality for treatment with curative intent. The response rate upon treatment with PD-1 antagonists in relation to the PD-L1 status is being investigated in 12 trials. Novel immune checkpoint modulators combined with the inhibition of the PD-1/PD-L1 axis or CTLA-4 have been set up in six trials. So far, only four studies that use immune checkpoint inhibition in HNSCC have presented results and all of these explored the inhibition of the PD-1/PD-L1 axis. The studies demonstrated overall response rates (ORR) in the range of 20%. These preliminary data suggest that a PD-L1 expression ≥1% is associated with a higher response rate compared to a PD-L1 expression ≤1%. The anti-PD-1-antibody pembrolizumab extended the duration of response in recurrent and/or metastatic (R/M) HNSCC (by approximately 53 weeks) in a phase Ib study. Therefore, pembrolizumab was granted accelerated approval for the treatment of platinum refractory R/M HNSCC by the FDA.
Numerous clinical trials are addressing the suitability and efficacy of immune checkpoint modulators in HNSCC with the predominant targets being the established immune checkpoint receptors PD-1/PD-L1 and CTLA-4. Recently, presented results have shown a survival benefit, a favourable safety profile and an extended duration of response in favour of using immune checkpoint modulation in R/M HNSCC.
近年来，免疫检查点抑制剂在癌症治疗领域取得了巨大进展。激活机体自身免疫系统为黑色素瘤和肺癌的治疗增添了一种全新且强大的治疗选择。此外，免疫疗法在其他恶性肿瘤中的潜在应用也在广泛探索中。
本综述总结了目前使用免疫检查点调节剂治疗头颈部癌（HNSCC）的临床研究。
系统综述。
对2010年起PubMed上关于免疫检查点抑制剂在HNSCC临床试验中的应用进行检索。在clinicaltrials.gov上进行了类似检索。此外，还筛选了美国临床肿瘤学会（ASCO）、欧洲肿瘤内科学会（ESMO）和美国癌症研究协会（AACR）年会的摘要。
共确定了45项在HNSCC中使用免疫检查点抑制剂的相关研究。在这些研究中，大多数使用靶向免疫检查点受体PD-1的拮抗抗体，单独使用或联合使用，大多与其他免疫调节抗体联合，如细胞毒性T淋巴细胞相关抗原4（CTLA-4）抑制剂。大多数研究仍在招募患者（26/45）。在初始治疗中，我们确定了16项使用检查点抑制作为新辅助/辅助治疗手段以达到治愈目的的研究。12项试验正在研究PD-1拮抗剂治疗时的缓解率与PD-L1状态的关系。六项试验设立了联合抑制PD-1/PD-L1轴或CTLA-4的新型免疫检查点调节剂。到目前为止，只有四项在HNSCC中使用免疫检查点抑制的研究公布了结果，且所有这些研究都探索了对PD-1/PD-L1轴的抑制。这些研究显示总体缓解率（ORR）在20%左右。这些初步数据表明，与PD-L1表达≤1%相比，PD-L1表达≥1%与更高的缓解率相关。在一项Ib期研究中，抗PD-1抗体帕博利珠单抗延长了复发和/或转移性（R/M）HNSCC的缓解持续时间（约53周）。因此，帕博利珠单抗被美国食品药品监督管理局（FDA）加速批准用于治疗铂类难治性R/M HNSCC。
众多临床试验正在探讨免疫检查点调节剂在HNSCC中的适用性和疗效，主要靶点是已确定的免疫检查点受体PD-1/PD-L1和CTLA-4。最近公布的结果显示，在R/M HNSCC中使用免疫检查点调节具有生存获益、良好的安全性和延长的缓解持续时间。
