程序性細胞死亡蛋白1（PD-1）抑制在肝細胞癌（HCC）中的應用

StephenW

Programmed cell death protein 1 (PD-1)-inhibition in hepatocellular carcinoma (HCC): a single center experience
Robert Mahn , Annabelle Vogt , Patrick Kupczyk , Farsaneh Sadeghlar , Katrin van Beekum , Robert Hüneburg , show all
Received 20 May 2020, Accepted 06 Jul 2020, Published online: 21 Jul 2020

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Abstract
Background

The prognosis for advanced Hepatocellular carcinoma (HCC)is still very poor. Despite initial usefulness of immune checkpoint inhibitor (PD-1), phase 3 trials failed to show significant benefit of PD-1 inhibition with nivolumab or pembrolizumab in the first and second line therapy of HCC. Clinical evidence of PD-1 inhibition in patients with advanced and heavily pretreated HCC outside clinical trials is extremely limited. In this study, we analyzed the clinical experience with PD-1 inhibition in patients with heavily pretreated HCC.
Methods

Between May 2016 and January 2019 14 patients with advanced and heavily pretreated HCC were treated with nivolumab or pembrolizumab at the University Hospital Bonn, Germany. Base line characteristics prior to immunotherapy, immunohistochemistry of different immunological markers, beneficial outcome and safety were recorded and retrospectively analyzed.
Results

Immunotherapy with PD-1 inhibition was well tolerated and resulted in significant clinical benefit as last line therapy. Median overall survival (OS) was 6.6 months (95%CI:3.9–11.8), progression-free survival (PFS) was 5.3 months (95%CI:2.4–11.7) and overall response rate (ORR) was 30.8%. One patient reached a complete remission.
Conclusions

Despite numerous pretreatments, PD-1 inhibition was well tolerated and showed clinical benefit in patients with heavily pretreated HCC.
Keywords: Hepatocellular carcinoma, immune checkpoint inhibition, nivolumab, PD-1 inhibition, pembrolizumab
Additional information
Funding
This work was supported by the following grants awarded to M.A. Gonzalez-Carmona: GO 1874/1-2 grant from the ‘Deutsche Forschungsgemeinschaft’ (DFG), BONFOR from the University of Bonn, grant number 109255 from the ‘Deutsche Krebshilfe’ (German Cancer Aid) and grant from the Reuthersche endowment fund of the University of Bonn.
Acknowledgements

The authors thank Ms. Kathrin Brinkmann and Ms. Sonja Hebold for their extremely valuable support and assistance in this work.
Disclosure statement

All authors approved the final version of the manuscript. None of the authors have any potential conflicts (financial, professional or personal) that are relevant to the manuscript. Maria A. Gonzalez-Carmona has contributed to advisory board for BMS, Eisai, Amgen, IPSEN and Roche.

StephenW

程序性細胞死亡蛋白1（PD-1）抑制在肝細胞癌（HCC）中的應用：單中心經驗
羅伯特·馬恩（Robert Mahn），安娜貝勒·沃格特（Annabelle Vogt），帕特里克·庫普齊克（Patrick Kupczyk），法薩內·薩德格拉爾（Farsaneh Sadeghlar），卡特琳·範比克姆（Katrin van Beekum），羅伯特·洪堡（RobertHüneburg）
2020年5月20日收到，2020年7月6日接受，在線發布：2020年7月21日

    下載引文https://doi.org/10.1080/00365521.2020.1794539 CrossMark徽標CrossMark

抽象
背景

晚期肝細胞癌（HCC）的預後仍然很差。儘管最初具有免疫檢查點抑製劑（PD-1）的作用，但3期試驗未能顯示出用nivolumab或pembrolizumab抑制PD-1在HCC的一線和二線治療中具有明顯的益處。在臨床試驗之外，晚期和高度預處理的HCC患者中PD-1抑制的臨床證據極為有限。在這項研究中，我們分析了嚴重預處理的HCC患者PD-1抑制的臨床經驗。
方法

在2016年5月至2019年1月之間，在德國波恩大學醫院對14例晚期HCC進行了嚴格預處理的患者接受了nivolumab或pembrolizumab治療。記錄並回顧性分析免疫治療前的基線特徵，不同免疫學標記物的免疫組織化學，有益結果和安全性。
結果

具有PD-1抑製作用的免疫療法具有良好的耐受性，並且作為最後一線療法具有明顯的臨床益處。中位總生存期（OS）為6.6個月（95％CI：3.9-11.8），無進展生存期（PFS）為5.3個月（95％CI：2.4-11.7），總緩解率（ORR）為30.8％。一名患者完全緩解。
結論

儘管進行了許多預處理，PD-1抑制仍具有良好的耐受性，並在高度預處理的HCC患者中顯示出臨床獲益。
關鍵詞：肝細胞癌，免疫檢查點抑制，nivolumab，PD-1抑制，派姆單抗
附加信息
資金
這項工作得到了岡薩雷斯·卡莫納（MA Gonzalez-Carmona）的以下贈款的支持：“ Deutsche Forschungsgemeinschaft”（DFG）的GO 1874 / 1-2贈款，波恩大學的BONFOR，“ Deutsche Krebshilfe”（德國）的贈款編號109255。癌症援助）和波恩大學Reuthersche捐贈基金的贈款。
致謝

作者感謝Kathrin Brinkmann女士和Sonja Hebold女士在這項工作中提供的寶貴幫助。
披露聲明

所有作者都批准了稿件的最終版本。沒有任何作者有與手稿有關的任何潛在衝突（財務，專業或個人）。瑪麗亞·岡薩雷斯·卡莫納（Maria A. Gonzalez-Carmona）為BMS，衛材，安進，IPSEN和羅氏公司的顧問委員會做出了貢獻。