Guigay Joël, Tahara Makoto, Licitra Lisa, Keilholz Ulrich, Friesland Signe, Witzler Pauline, Mesía Ricard
Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France.
Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Tokyo, Japan.
Front Oncol. 2019 Aug 21;9:668. doi: 10.3389/fonc.2019.00668. eCollection 2019.
The addition of cetuximab to platinum-based chemotherapy (cisplatin or carboplatin plus 5-fluorouracil [5-FU]), followed by maintenance cetuximab until disease progression (EXTREME), resulted in the first regimen to yield significantly improved survival outcomes in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in over 30 years. Currently, the EXTREME regimen is a guideline-recommended treatment in the first-line R/M setting, and, therefore, it is used as a control arm in all new first-line, phase 3 immunotherapy trials. More recently, new checkpoint inhibitor approaches have emerged and are changing the treatment landscape for PD-L1-positive patients with R/M SCCHN. Additionally, alternative chemotherapy backbones in R/M SCCHN are continually investigated. Replacing 5-FU with a taxane in the EXTREME regimen seeks to take advantage of the potential immunogenic and proapoptotic synergy between cetuximab and docetaxel or paclitaxel. These cetuximab-, platinum-, and taxane-based treatments have demonstrated promising survival results and cytoreductive properties in single-arm studies. Thus, these combination treatments may be of importance to patients with high tumor burden and dangerous site involvements (e.g., causing bleeding, suffocation, dysphagia, or ulceration), in whom symptom relief is a key treatment goal. TPExtreme is the first large, randomized trial comparing a cetuximab, platinum, and taxane combination regimen with EXTREME. Currently, the substitution of 5-FU with a taxane is a feasible and clinically beneficial option for patients with contraindications to 5-FU. The TPEx regimen appears to be a new option in first-line R/M SCCHN, with a shorter time on CT and significantly lower toxicity than the EXTREME regimen. For patients with R/M disease in whom further cisplatin- or carboplatin-based treatment is unsuitable, or whose disease has already progressed on first-line R/M therapy, treatment options such as cetuximab plus a taxane, which capitalize on the combinative ability of the 2 agents, can be considered. Notably, it is as of yet unknown what second-line treatments may be suitable to follow a checkpoint inhibitor-based first-line therapy.
在铂类化疗（顺铂或卡铂加5-氟尿嘧啶[5-FU]）基础上加用西妥昔单抗，随后持续使用西妥昔单抗直至疾病进展（EXTREME方案），这产生了30多年来首个在复发性和/或转移性头颈部鳞状细胞癌（R/M SCCHN）一线治疗中显著改善生存结果的方案。目前，EXTREME方案是一线R/M治疗中指南推荐的治疗方法，因此，在所有新的一线3期免疫治疗试验中它被用作对照臂。最近，新的检查点抑制剂方法出现了，正在改变PD-L1阳性R/M SCCHN患者的治疗格局。此外，R/M SCCHN中替代化疗方案也在不断研究。在EXTREME方案中用紫杉烷替代5-FU旨在利用西妥昔单抗与多西他赛或紫杉醇之间潜在的免疫原性和促凋亡协同作用。这些基于西妥昔单抗、铂和紫杉烷的治疗在单臂研究中已显示出有前景的生存结果和减瘤特性。因此，这些联合治疗对于肿瘤负荷高和有危险部位受累（如导致出血、窒息、吞咽困难或溃疡）的患者可能很重要，在这些患者中，缓解症状是关键的治疗目标。TPExtreme是首个比较西妥昔单抗、铂和紫杉烷联合方案与EXTREME方案的大型随机试验。目前，对于有5-FU禁忌证的患者，用紫杉烷替代5-FU是一种可行且具有临床益处的选择。TPEx方案似乎是一线R/M SCCHN中的一个新选择，与EXTREME方案相比，CT时间更短且毒性显著更低。对于R/M疾病患者，若进一步进行基于顺铂或卡铂的治疗不合适，或其疾病在一线R/M治疗中已经进展，可以考虑西妥昔单抗加紫杉烷等利用这两种药物联合能力的治疗选择。值得注意的是，目前尚不清楚基于检查点抑制剂的一线治疗后适合采用何种二线治疗。
