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抗PD-1疗法治疗黑色素瘤的安全性。

The safety of anti PD-1 therapeutics for the treatment of melanoma.

作者信息

Ramelyte Egle, Schindler Sabrina A, Dummer Reinhard

机构信息

a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland.

b Centre of Dermatovenereology , Vilnius University Hospital Santariskiu klinikos , Vilnius , Lithuania.

出版信息

Expert Opin Drug Saf. 2017 Jan;16(1):41-53. doi: 10.1080/14740338.2016.1248402. Epub 2016 Oct 24.

Abstract

The introduction of immunotherapies into clinical practice has substantially improved the prognosis of metastatic melanoma patients as well as patients suffering from other cancers. The two FDA-approved checkpoint inhibitors against PD-1 (nivolumab and pembrolizumab) have been shown to significantly improve patient survival while being less toxic than previous treatment options. Areas covered: The current scientific literature on safety and adverse events (AEs) related to anti-PD-1 therapies has been investigated with special attention to case reports and to the latest results announced at the major clinical cancer and melanoma meetings, including ASCO (American Society of Clinical Oncology), ESMO (European Society of medical Oncology) and EADO (European Association of Dermato-Oncology) annual meetings. Expert opinion: Even though anti-PD-1 therapies are better tolerated than conventional chemo- or other immune-therapies, they still induce a plethora of AEs. Given the mechanism of action, it is supposed that most if not all of them are immune related. Fortunately, the majority are mild and manageable. However, due to the increase in patients' life expectancy, there is a substantial need to understand and prevent severe cutaneous, pulmonary, neurological and other AEs which have major impact on the quality of life. The safety profile after long term use of these medications is still unclear. In addition, non-steroid based immune interventions to control autoimmunity are still to be developed.

摘要

免疫疗法引入临床实践后,已显著改善了转移性黑色素瘤患者以及其他癌症患者的预后。美国食品药品监督管理局(FDA)批准的两种抗PD-1检查点抑制剂(纳武单抗和派姆单抗)已被证明可显著提高患者生存率,且毒性低于以往的治疗方案。涵盖领域:对当前关于抗PD-1疗法相关安全性和不良事件(AE)的科学文献进行了研究,特别关注病例报告以及在主要临床癌症和黑色素瘤会议上公布的最新结果,包括美国临床肿瘤学会(ASCO)、欧洲医学肿瘤学会(ESMO)和欧洲皮肤肿瘤学会(EADO)年会。专家意见:尽管抗PD-1疗法比传统化疗或其他免疫疗法耐受性更好,但它们仍会引发大量不良事件。鉴于其作用机制,推测其中大多数(即便不是全部)不良事件与免疫相关。幸运的是,大多数不良事件较为轻微且易于处理。然而,由于患者预期寿命的增加,迫切需要了解和预防对生活质量有重大影响的严重皮肤、肺部、神经及其他不良事件。这些药物长期使用后的安全性概况仍不明确。此外,控制自身免疫的非类固醇类免疫干预措施仍有待开发。

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