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本文引用的文献

1
Molecular pathways in vulvar squamous cell carcinoma: implications for target therapeutic strategies.外阴鳞状细胞癌中的分子通路:对靶向治疗策略的影响。
J Cancer Res Clin Oncol. 2020 Jul;146(7):1647-1658. doi: 10.1007/s00432-020-03226-6. Epub 2020 Apr 25.
2
Cancer statistics, 2020.癌症统计数据,2020 年。
CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
3
Overexpression of p16 Serves as Prognostic Marker in Squamous Cell Vulvar Cancer Patients Treated With Radiotherapy Irrespective of HPV-Status.无论HPV状态如何,p16过表达作为接受放疗的外阴鳞状细胞癌患者的预后标志物。
Front Oncol. 2019 Sep 11;9:891. doi: 10.3389/fonc.2019.00891. eCollection 2019.
4
Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva.外阴鳞癌中 PD-L1 和 PD-1 表达的临床影响。
J Cancer Res Clin Oncol. 2019 Jun;145(6):1651-1660. doi: 10.1007/s00432-019-02915-1. Epub 2019 Apr 10.
5
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study.帕博利珠单抗治疗既往治疗的晚期宫颈癌的疗效和安全性:来自 II 期 KEYNOTE-158 研究的结果。
J Clin Oncol. 2019 Jun 10;37(17):1470-1478. doi: 10.1200/JCO.18.01265. Epub 2019 Apr 3.
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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy.不断发展的免疫检查点抑制剂治疗生物标志物。
Nat Rev Cancer. 2019 Mar;19(3):133-150. doi: 10.1038/s41568-019-0116-x.
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T-Cell-Inflamed Gene-Expression Profile, Programmed Death Ligand 1 Expression, and Tumor Mutational Burden Predict Efficacy in Patients Treated With Pembrolizumab Across 20 Cancers: KEYNOTE-028.T 细胞炎症基因表达谱、程序性死亡配体 1 表达和肿瘤突变负担可预测帕博利珠单抗治疗 20 种癌症患者的疗效:KEYNOTE-028。
J Clin Oncol. 2019 Feb 1;37(4):318-327. doi: 10.1200/JCO.2018.78.2276. Epub 2018 Dec 13.
8
PD-L1 and IDO expression in cervical and vulvar invasive and intraepithelial squamous neoplasias: implications for combination immunotherapy.PD-L1 和 IDO 在宫颈和外阴浸润性及上皮内鳞状肿瘤中的表达:对联合免疫治疗的影响。
Histopathology. 2019 Jan;74(2):256-268. doi: 10.1111/his.13723. Epub 2018 Oct 29.
9
Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature.派姆单抗治疗复发性外阴鳞状细胞癌:病例报告及文献综述
Gynecol Obstet Invest. 2019;84(1):94-98. doi: 10.1159/000491090. Epub 2018 Jul 17.
10
PD-L1 receptor expression in vulvar carcinomas is HPV-independent.PD-L1 受体在外阴癌中的表达与 HPV 无关。
Virchows Arch. 2018 Oct;473(4):513-516. doi: 10.1007/s00428-018-2364-7. Epub 2018 May 8.

外阴鳞状细胞癌(VSCC)的靶向治疗方法:病例系列和文献复习。

Targeted Therapeutic Approaches in Vulvar Squamous Cell Cancer (VSCC): Case Series and Review of the Literature.

机构信息

Department of Gynecology, University Medical Center Hamburg-EppendorfHamburgGermany.

Department of Pathology, University Medical Center Hamburg-EppendorfHamburgGermany.

出版信息

Oncol Res. 2021 Mar 16;28(6):645-659. doi: 10.3727/096504020X16076861118243. Epub 2020 Dec 11.

DOI:10.3727/096504020X16076861118243
PMID:33308371
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7962928/
Abstract

Therapeutic options in recurrent or metastasized vulvar squamous cell cancer (VSCC) not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 20132019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE, Web of Science, Scopus, and OVID database search was performed using the terms: vulvar cancer AND targeted therapy, erlotinib, EGFR, bevacizumab, VEGF, pembrolizumab, or immunotherapy. Twelve of 291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinum-based chemotherapy was applied to all patients [median 3.5 previous lines (range 25)]. In the erlotinib subgroup, two of five patients (40%) achieved stable disease (SD), while two patients (2/5, 40%) experienced partial response (PR). Treatment was given as monotherapy in second/third line for a median of 3.4 months (range 26 months). Bevacizumab (n=9) was given as maintenance therapy after platinum-based first-line chemotherapy (9/9); best response was complete response (CR) (n=2/9 22.2%). Median duration of treatment was 7 months (range 413 months) with two patients still under ongoing treatment. Best response in the pembrolizumab (n=3) subset was SD (n=1/3 33%). Treatment was given as monotherapy in second/third line for a median of 3.3 months (range 34 months). Nine of 12 patients (75%) experienced treatment-related adverse events (TRAEs), most commonly grade 1/2. Rapidly evolving antibody treatments have proven clinical benefit especially in HPV-driven tumor entities; however, clinical investigations in VSCC are still limited. These reported cases provide evidence for the clinical utility and feasibility while ensuring an acceptable safety profile.

摘要

在不适合放疗或根治性手术的复发性或转移性外阴鳞状细胞癌 (VSCC) 患者中,治疗选择有限。靶向治疗的证据很少。对 2013 年至 2019 年在汉堡-埃彭多夫妇科癌症中心治疗的所有 VSCC 患者进行了回顾性评估,以确定靶向治疗方法。此外,还使用以下术语在 MEDLINE、EMBASE、Web of Science、Scopus 和 OVID 数据库中进行了搜索:外阴癌和靶向治疗、厄洛替尼、EGFR、贝伐单抗、VEGF、pembrolizumab 或免疫疗法。在我们的机构中,有 12 名(4.1%)VSCC 患者接受了至少一种靶向治疗。此前,所有患者均应用了一种或多种铂类化疗药物[中位数为 3.5 线(范围 25)]。在厄洛替尼组中,5 名患者中有 2 名(40%)病情稳定(SD),2 名患者(2/5,40%)部分缓解(PR)。治疗作为二线/三线药物单药治疗,中位时间为 3.4 个月(范围 26 个月)。贝伐单抗(n=9)在铂类一线化疗后作为维持治疗(9/9);最佳反应为完全缓解(CR)(n=2/9,22.2%)。中位治疗时间为 7 个月(范围 413 个月),有 2 名患者仍在接受治疗。pembrolizumab(n=3)组的最佳反应为 SD(n=1/3,33%)。治疗作为二线/三线药物单药治疗,中位时间为 3.3 个月(范围 34 个月)。12 名患者中有 9 名(75%)出现治疗相关不良事件(TRAEs),最常见的是 1/2 级。快速发展的抗体治疗已证明具有临床获益,尤其是在 HPV 驱动的肿瘤实体中;然而,VSCC 的临床研究仍然有限。这些报告的病例提供了临床应用的证据和可行性,同时确保了可接受的安全性。