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肺癌中免疫检查点抑制剂的延长给药间隔策略:它能在新冠疫情期间持续有效吗?

Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic?

作者信息

Sehgal Kartik, Costa Daniel B, Rangachari Deepa

机构信息

Division of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.

出版信息

Front Oncol. 2020 Jun 23;10:1193. doi: 10.3389/fonc.2020.01193. eCollection 2020.

Abstract

Patients with lung cancer are particularly vulnerable to complications from coronavirus disease-2019 (COVID-19). Recurrent hospital visits and hospital admission are potential risk factors for acquiring infection with its causative pathogen, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As immune checkpoint inhibitors (ICIs) constitute the therapeutic backbone for the vast majority of patients with advanced lung cancer in the absence of actionable driver oncogenes, there have been intense discussions within the oncology community regarding risk-benefit of delaying these treatments or use of alternative extended-interval treatment strategies to minimize the risk of viral transmission secondary to unintended nosocomial exposures. In the midst of the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) granted accelerated approval for extended-interval strategy of pembrolizumab at a dose of 400 mg every 6 weeks for all already approved oncologic indications. Herein, we summarize the evidence from the pharmacokinetic modeling/simulation studies supporting extended-interval dosing strategies for the ICIs used in lung cancer. We further review the evolving clinical evidence behind these approaches and predict that they will continue to be used in routine practice even long after the pandemic, particularly for patients with durable disease control.

摘要

肺癌患者尤其容易出现2019冠状病毒病(COVID-19)并发症。反复就诊和住院是感染其致病病原体严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的潜在危险因素。由于在没有可操作的驱动癌基因的情况下,免疫检查点抑制剂(ICI)是绝大多数晚期肺癌患者的治疗支柱,肿瘤学界一直在激烈讨论延迟这些治疗的风险效益,或使用替代的延长间隔治疗策略,以尽量减少因意外的医院内暴露而导致病毒传播的风险。在COVID-19大流行期间,美国食品药品监督管理局(FDA)加速批准了帕博利珠单抗的延长间隔策略,即每6周服用400 mg,用于所有已获批的肿瘤适应症。在此,我们总结了药代动力学建模/模拟研究的证据,这些证据支持肺癌中使用的ICI的延长间隔给药策略。我们进一步回顾了这些方法背后不断演变的临床证据,并预测即使在大流行很久之后,它们仍将继续用于常规治疗,特别是对于疾病得到持久控制的患者。

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