Brain Tumor Stem Cell Laboratory, Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd. S, Jacksonville, FL, 32224, USA.
Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA.
Target Oncol. 2021 May;16(3):325-337. doi: 10.1007/s11523-021-00814-5. Epub 2021 Apr 24.
Chordoma is a rare but devastating tumor that arises in the cranial skull base or spine. There are currently no US Food and Drug Administration-approved targeted therapies for chordoma, and little understanding of whether using more than one therapy has benefit over monotherapy.
The objective of this study was to systematically review the current status of clinical trials completed for patients with chordoma to determine if multimodal therapy offers a benefit in progression-free survival over monomodal therapy.
We performed a systematic review of the literature according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to review the available clinical trials of targeted therapy for chordoma. We compiled the clinical data to determine if there is a benefit of multimodal therapy over monotherapy.
Our search resulted in 11 clinical trials including 270 patients with advanced chordoma who were treated with targeted therapies. The most commonly employed targeted therapies acted within the following pathways: platelet-derived growth factor receptor (187 patients), vascular endothelial growth factor (66 patients), and mammalian target of rapamycin (43 patients). Reported progression-free survival for included studies ranged from 2.5 to 58 months, with the longest progression-free survival in a trial that included a platelet-derived growth factor receptor inhibitor, nilotinib, and concurrent radiotherapy (58.2 months). There was a higher range of progression-free survival for trials treating patients with multimodal therapy (10.2-14 months vs 2.5-9.2 months, except for a monotherapy trial published in 2020 with a progression-free survival of 18 months), and those published in 2018 or later (14-58.2 months vs 2.5-10.2 months). Only 23% of patients with chordoma in published clinical trials have been treated with multimodal therapy.
Progression-free survival may be enhanced by the use of targeted therapy with concurrent radiotherapy, use of multimodal therapy, and use of newer targeted therapy. Future clinical trials should consider use of concurrent radiotherapy and multimodal therapy for patients with advanced chordoma.
脊索瘤是一种罕见但具有破坏性的肿瘤，发生在颅底或脊柱。目前，美国食品和药物管理局尚未批准用于脊索瘤的靶向治疗方法，并且对于是否使用一种以上的治疗方法比单一疗法更有优势知之甚少。
本研究旨在系统回顾已完成的脊索瘤患者临床试验的现状，以确定多模式治疗在无进展生存期方面是否优于单一疗法。
我们根据系统评价和荟萃分析的首选报告项目 (PRISMA) 指南进行了文献系统回顾，以回顾用于脊索瘤的靶向治疗的现有临床试验。我们汇总了临床数据，以确定多模式治疗是否优于单一疗法。
我们的搜索结果包括 11 项临床试验，共纳入 270 例接受靶向治疗的晚期脊索瘤患者。最常使用的靶向治疗作用于以下途径：血小板衍生生长因子受体 (187 例患者)、血管内皮生长因子 (66 例患者) 和哺乳动物雷帕霉素靶蛋白 (43 例患者)。纳入研究报告的无进展生存期范围为 2.5 至 58 个月，最长的无进展生存期是在一项包括血小板衍生生长因子受体抑制剂尼洛替尼和同步放疗的试验中 (58.2 个月)。接受多模式治疗的试验的无进展生存期范围较高 (10.2-14 个月与 2.5-9.2 个月，2020 年发表的一项单一疗法试验除外，其无进展生存期为 18 个月)，且发表于 2018 年或之后的试验 (14-58.2 个月与 2.5-10.2 个月)。发表的临床试验中只有 23%的脊索瘤患者接受了多模式治疗。
靶向治疗联合放疗、多模式治疗和使用新型靶向治疗可能会提高无进展生存期。未来的临床试验应考虑为晚期脊索瘤患者使用同步放疗和多模式治疗。
