Daste Amaury, Domblides Charlotte, Gross-Goupil Marine, Chakiba Camille, Quivy Amandine, Cochin Valérie, de Mones Erwan, Larmonier Nicolas, Soubeyran Pierre, Ravaud Alain
Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital-CHU Bordeaux, France.
Department of Medical Oncology, Hôpital Saint-André, Bordeaux University Hospital-CHU Bordeaux, France; University of Bordeaux, Bordeaux, France; ImmunoConcEpt, CNRS UMR 5164, Bordeaux University, Bordeaux 33076, France.
Eur J Cancer. 2017 Sep;82:155-166. doi: 10.1016/j.ejca.2017.05.044. Epub 2017 Jul 6.
Immune checkpoint inhibitors, including targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte antigen 4 pathways, are a new type of cancer treatment. This approach of targeting the immune system has demonstrated dramatic efficacy for several cancers, and various drugs have been approved by health authorities and are used in clinical practice. Elderly patients (≥65 years) represent most of the cancers diagnosed and deaths by age group, with an increase expected over the next decade. However, this subgroup of patients is under-represented in clinical trials. Ageing is also associated with a decrease in the effectiveness of the immune system and in alterations to it. Few specific trials have been carried out for immunotherapy in elderly people, with most patients considered to be fit. In this review, we discuss the impact of ageing and immunosenescence on immune system functions, and we assess the safety and efficacy of immune checkpoint inhibitors in elderly patients, principally from the data of pivotal clinical trials with subgroup analysis. Tolerance in elderly patients seems similar to younger people, but efficacy seems different between younger and elderly patients according to the type of cancer, some showing no difference and others less efficacy in the elderly subgroup. However, the numbers in elderly groups are small and more investigation is needed, with specific clinical trials for elderly cancer patients.
免疫检查点抑制剂,包括针对程序性细胞死亡蛋白1、程序性细胞死亡配体1和细胞毒性T淋巴细胞相关抗原4通路的抑制剂,是一种新型的癌症治疗方法。这种针对免疫系统的方法已在几种癌症中显示出显著疗效,多种药物已获卫生当局批准并应用于临床实践。老年患者(≥65岁)在各年龄组的癌症诊断和死亡病例中占大多数,预计在未来十年这一比例还会上升。然而,这一患者亚组在临床试验中的代表性不足。衰老还与免疫系统有效性的降低及其改变有关。针对老年人免疫治疗的特定试验很少,大多数患者被认为身体状况良好。在本综述中,我们讨论衰老和免疫衰老对免疫系统功能的影响,并主要根据关键临床试验的数据及亚组分析评估免疫检查点抑制剂在老年患者中的安全性和疗效。老年患者的耐受性似乎与年轻人相似,但根据癌症类型,年轻患者和老年患者的疗效似乎有所不同,一些癌症在老年亚组中显示无差异,而另一些则疗效较差。然而,老年组的病例数较少,需要更多研究,尤其是针对老年癌症患者的特定临床试验。