背景:肺癌是老年人的癌症,诊断时的中位年龄为71岁。超过三分之一的被诊断患有肺癌的人超过75岁。免疫检查点抑制剂(ICI)是针对免疫系统中称为程序性细胞死亡1/程序性细胞死亡配体1(PD-1/PD-L1)途径的途径的特殊抗体。这些抗体通过阻断癌细胞用来避免被免疫系统攻击的信号来帮助免疫系统对抗癌细胞。ICI改变了肺癌患者的治疗方法。特别是,对于先前未治疗的晚期非小细胞肺癌(NSCLC)患者,目前的一线治疗现在包括ICIs加铂类化疗,而不是单独的铂类化疗,无论其PD-L1表达状态如何。然而,随着人们年龄的增长,他们的免疫系统发生变化,在其T细胞反应中变得不那么有效。这引发了关于ICI在老年人中工作的问题。
目的:评估免疫检查点抑制剂(ICIs)联合铂类化疗与铂类化疗(有或没有贝伐单抗)在65岁以上初治晚期NSCLC患者中的效果。
方法:我们搜索了Cochrane肺癌组试验注册,中部,MEDLINE,Embase,另外两个审判登记簿,和药品监管机构的网站。最近的搜索日期是2023年8月23日。我们还检查了2019年至2023年8月七个癌症组织会议的参考文献和摘要。
方法:我们纳入了随机对照试验(RCT),该试验报告了在基于铂的化疗中加入ICIs的疗效和安全性,与65岁及以上以前未接受过治疗的患者相比,在基于铂的化疗中加入ICIs的疗效和安全性。所有数据均来自国际多中心研究,涉及经组织学证实的晚期NSCLC成人,他们以前未接受过任何针对其晚期疾病的全身抗癌治疗。
方法:我们使用了Cochrane预期的标准方法学程序。我们的主要结果是总生存率和治疗相关的不良事件(3级或更高)。我们的次要结果是无进展生存期,客观反应率,响应时间,响应的持续时间,和健康相关生活质量(HRQoL)。
结果:我们纳入了17项主要研究,共有4276人参加,在评论综合中。我们确定了九项正在进行的研究,并将一项研究列为“等待分类”。17项研究中有12项包括75岁以上的人,占他们参与者的9%到13%。我们认为一些研究对随机化过程中产生的偏倚风险有“一些担忧”,偏离预期的干预措施,或衡量结果。由于存在偏差的风险,证据确定性的总体等级评级从中等到低不等。不精确,或不一致。65岁及以上的人群与仅含铂的化疗相比,在含铂的化疗中添加ICI可能会增加总生存率(风险比(HR)0.78,95%置信区间(CI)0.70至0.88;8项研究,2093名参与者;中等确定性证据)。只有一项研究报告了治疗相关不良事件的数据(3级或更高)。治疗相关不良事件的频率在两个治疗组之间可能没有差异(风险比(RR)1.09,95%CI0.89~1.32;1项研究,127名参与者;低确定性证据)。在铂类化疗中加入ICI可能会改善无进展生存期(HR0.61,95%CI0.54~0.68;7项研究,1885名参与者;中等确定性证据)。65至75岁的人,与单用铂类化疗相比,在铂类化疗中加入ICI可能会改善总生存率(HR0.75,95%CI0.65至0.87;6项研究,1406名参与者;中度确定性证据)。只有一项研究报告了治疗相关不良事件的数据(3级或更高)。与仅接受铂类化疗的患者相比,接受ICIs加铂类化疗的患者治疗相关不良事件的频率可能会增加(RR1.47,95%CI1.02至2.13;1项研究,97名参与者;中等确定性证据)。在铂类化疗中加入ICI可能会改善无进展生存期(HR0.64,95%CI0.57~0.73;8项研究,1466名参与者;中等确定性证据)。75岁及以上的人群与单用铂类化疗相比,使用ICIs联合铂类化疗的患者的总生存率可能没有差异(HR0.90,95%CI0.70至1.16;4项研究,297名参与者;低确定性证据)。在这个年龄组中没有关于治疗相关不良事件的数据。ICI联合铂类化疗对无进展生存期的影响尚不确定(HR0.83,95%CI0.51~1.36;3项研究,226名参与者;非常低的确定性证据)。只有三项研究评估了客观反应率。响应的时间,响应的持续时间,和健康相关的生活质量,我们还没有任何证据。
结论:与单用铂类化疗相比,在铂类化疗中加入ICI可能会导致更高的总生存率和无进展生存率,没有增加治疗相关的不良事件(3级或更高),65岁及以上的晚期NSCLC患者。这些数据基于65至75岁参与者主导的研究结果。然而,该分析还提示,在总生存期和无进展生存期方面报告的改善可能未见于75岁以上人群.
BACKGROUND: Lung cancer is a cancer of the elderly, with a median age at diagnosis of 71. More than one-third of people diagnosed with lung cancer are over 75 years old. Immune checkpoint inhibitors (ICIs) are special antibodies that target a pathway in the immune system called the programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. These antibodies help the immune system fight cancer cells by blocking signals that cancer cells use to avoid being attacked by the immune system. ICIs have changed the treatment of people with lung cancer. In particular, for people with previously-untreated advanced non-small cell lung cancer (NSCLC), current first-line treatment now comprises ICIs plus platinum-based chemotherapy, rather than platinum-based chemotherapy alone, regardless of their PD-L1 expression status. However, as people age, their immune system changes, becoming less effective in its T cell responses. This raises questions about how well ICIs work in older adults.
OBJECTIVE: To assess the effects of immune checkpoint inhibitors (ICIs) in combination with platinum-based chemotherapy compared to platinum-based chemotherapy (with or without bevacizumab) in treatment-naïve adults aged 65 years and older with advanced NSCLC.
METHODS: We searched the Cochrane Lung Cancer Group Trial Register, CENTRAL, MEDLINE, Embase, two other trial registers, and the websites of drug regulators. The latest search date was 23 August 2023. We also checked references and searched abstracts from the meetings of seven cancer organisations from 2019 to August 2023.
METHODS: We included randomised controlled trials (RCTs) that reported on the efficacy and safety of adding ICIs to platinum-based chemotherapy compared to platinum-based chemotherapy alone for people 65 years and older who had not previously been treated. All data emanated from international multicentre studies involving adults with histologically-confirmed advanced NSCLC who had not received any previous systemic anticancer therapy for their advanced disease.
METHODS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival and treatment-related adverse events (grade 3 or higher). Our secondary outcomes were progression-free survival, objective response rate, time to response, duration of response, and health-related quality of life (HRQoL).
RESULTS: We included 17 primary studies, with a total of 4276 participants, in the review synthesis. We identified nine ongoing studies, and listed one study as \'awaiting classification\'. Twelve of the 17 studies included people older than 75 years, accounting for 9% to 13% of their participants. We rated some studies as having \'some concerns\' for risk of bias arising from the randomisation process, deviations from the intended interventions, or measurement of the outcome. The overall GRADE rating for the certainty of the evidence ranged from moderate to low because of the risk of bias, imprecision, or inconsistency. People aged 65 years and older The addition of ICIs to platinum-based chemotherapy probably increased overall survival compared to platinum-based chemotherapy alone (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.70 to 0.88; 8 studies, 2093 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events may not differ between the two treatment groups (risk ratio (RR) 1.09, 95% CI 0.89 to 1.32; 1 study, 127 participants; low-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improves progression-free survival (HR 0.61, 95% CI 0.54 to 0.68; 7 studies, 1885 participants; moderate-certainty evidence). People aged 65 to 75 years, inclusive The addition of ICIs to platinum-based chemotherapy probably improved overall survival compared to platinum-based chemotherapy alone (HR 0.75, 95% CI 0.65 to 0.87; 6 studies, 1406 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events probably increased in people treated with ICIs plus platinum-based chemotherapy compared to those treated with platinum-based chemotherapy alone (RR 1.47, 95% CI 1.02 to 2.13; 1 study, 97 participants; moderate-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improved progression-free survival (HR 0.64, 95% CI 0.57 to 0.73; 8 studies, 1466 participants; moderate-certainty evidence). People aged 75 years and older There may be no difference in overall survival in people treated with ICIs combined with platinum-based chemotherapy compared to platinum-based chemotherapy alone (HR 0.90, 95% CI 0.70 to 1.16; 4 studies, 297 participants; low-certainty evidence). No data on treatment-related adverse events were available in this age group. The effect of combination ICI and platinum-based chemotherapy on progression-free survival is uncertain (HR 0.83, 95% CI 0.51 to 1.36; 3 studies, 226 participants; very low-certainty evidence). Only three studies assessed the objective response rate. For time to response, duration of response, and health-related quality of life, we do not have any evidence yet.
CONCLUSIONS: Compared to platinum-based chemotherapy alone, adding ICIs to platinum-based chemotherapy probably leads to higher overall survival and progression-free survival, without an increase in treatment-related adverse events (grade 3 or higher), in people 65 years and older with advanced NSCLC. These data are based on results from studies dominated by participants between 65 and 75 years old. However, the analysis also suggests that the improvements reported in overall survival and progression-free survival may not be seen in people older than 75 years.