Chung Clement
Baylor Scott and White Medical Center-College Station, College Station, TX, USA.
J Oncol Pharm Pract. 2019 Apr;25(3):663-673. doi: 10.1177/1078155218786365. Epub 2018 Jul 12.
Although programmed death-ligand 1 is currently the best available biomarker for first-line therapy with pembrolizumab for patients with non-small cell lung cancer and is a required companion test approved by the US Food and Drug Administration, programmed death-ligand 1 testing is an option (as a complementary test) for patients treated with nivolumab, atezolizumab, and durvalumab. Programmed death-ligand 1 expression is continuously variable and dynamic in the tumor microenvironment. Due to the complex molecular and cellular interactions involved in immune response, a single biomarker may not be sufficient to predict response to cancer immunotherapy. Integration of multiple tumor, immune response, and genomic parameters is likely to influence the future interpretation of biomarker-based treatment outcomes. This article, in a case-based format, concisely summarizes most up-to-date evidence in answering some commonly seen clinical controversies of cancer immunotherapy, in terms of (i) the predictive value of programmed death-ligand 1 as a biomarker; (ii) whether the use of steroids with checkpoint inhibitors will decrease efficacy of the latter; (iii) selection of patients for cancer immunotherapy based on immune-based response criteria, and (iv) whether the use of influenza vaccine with checkpoint inhibitors is considered safe. Until more robust, long-term prospective clinical data are available, these discussions may serve as a starting point for pharmacists to gain timely and effective management of these realistic issues.
尽管程序性死亡配体1目前是晚期非小细胞肺癌患者一线使用帕博利珠单抗治疗时最佳的生物标志物,且是美国食品药品监督管理局批准的必需伴随诊断检测,但程序性死亡配体1检测对于接受纳武利尤单抗、阿特珠单抗和度伐利尤单抗治疗的患者而言是一种选择(作为补充检测)。程序性死亡配体1的表达在肿瘤微环境中是持续可变且动态变化的。由于免疫反应涉及复杂的分子和细胞相互作用,单一生物标志物可能不足以预测癌症免疫治疗的反应。整合多种肿瘤、免疫反应和基因组参数可能会影响未来基于生物标志物的治疗结果的解读。本文以病例为基础的形式,简要总结了回答癌症免疫治疗一些常见临床争议的最新证据,包括:(i)程序性死亡配体1作为生物标志物的预测价值;(ii)联用类固醇与检查点抑制剂是否会降低后者的疗效;(iii)根据基于免疫的反应标准选择癌症免疫治疗的患者;以及(iv)联用流感疫苗与检查点抑制剂是否被认为是安全的。在获得更有力的长期前瞻性临床数据之前,这些讨论可作为药师及时有效管理这些实际问题的起点。