■随机临床试验(RCT)是批准新疗法的主要依据。然而,严格的纳入标准通常会导致他们偏离日常临床实践。真实世界(RW)证据具有补充作用,填补了治疗效果与其有效性之间的差距。免疫检查点抑制剂(ICIs)改变了非小细胞肺癌(NSCLC)的治疗方案;免疫相关不良事件(irAEs)可能成为危及生命的事件。当没有及时管理。多年来,我们对irAE的RW影响进行了系统评价和荟萃分析。
■系统评价集中于局部晚期或转移性NSCLC患者发生的irAE,在RW设置下用ICIs治疗。从1996年到2022年8月,我们查询了两个电子数据库(Embase和Medline)。然后,我们进行了一项荟萃分析,将结果分为两个队列(2015-2018年和2019-2021年)。我们描述了任何或严重等级(G)的irAE患者的患病率。估计值以比例表示,直到小数点后两位(效果大小,ES).感兴趣的IrAE是那些涉及皮肤的,肝脏,内分泌系统或胃肠道系统。
■总的来说,对5,439例患者的21项RW研究纳入了定量和定性综合。在2015-2018年的亚组中,G≥3个irAE的患病率略低,而两个时期任何级别的irAE的患病率相似。总的来说,我们观察到胃肠道的ES较高,肝和肺irAE,据报道,皮肤或内分泌IRAE的ES较低。在21项研究中,有10项报告了内分泌irAE,最近的研究略有增加,而皮肤毒性主要是在两个研究中报道的,在第一个时间段内。肺,肺胃肠,和肝毒性,随着时间的推移,ES的分布更加不均匀。
■我们的研究结果表明,在我们的荟萃分析中检查的两个日历周期中,irAE的频率保持稳定。这一发现表明,RW数据可能无法识别检测和管理irAE的潜在学习曲线。
UNASSIGNED: Randomized clinical trials (RCTs) represent the mainstay for the approval of new treatments. However, stringent inclusion criteria often cause them to depart from the daily clinical practice. Real-world (RW) evidence have a complementing role, filling the gap between the efficacy of a treatment and its effectiveness. Immune checkpoint inhibitors (ICIs) have changed the treatment scenario for non-small cell lung cancer (NSCLC); immune-related adverse events (irAEs) could become life-threatening events, when not timely managed. We performed a systematic
review and meta-analysis on the RW impact of irAEs through the years.
UNASSIGNED: The systematic
review focused on irAEs occurred in locally advanced or metastatic NSCLC patients, treated with ICIs in a RW setting. We queried two electronic databases (Embase and Medline) from 1996 to August 2022. We then conducted a meta-analysis dividing the results in two cohorts (2015-2018 and 2019-2021). We described the prevalence of patients with irAEs of any or severe grade (G). Estimates were expressed as proportions up to the second decimal point (effect size, ES). IrAEs of interest were those involving the skin, the liver, the endocrine system or the gastro-intestinal system.
UNASSIGNED: Overall, 21 RW studies on 5,439 patients were included in the quantitative and qualitative synthesis. The prevalence of G≥3 irAEs was slightly lower in the 2015-2018 subgroup, while the prevalence of irAEs of any grade was similar for both periods. Overall, we observed a higher ES for gastrointestinal, hepatic and lung irAEs, while a lower ES was reported for skin or endocrine irAEs. Endocrine irAEs were reported in 10 out of 21 studies, with a slight increase in the most recent studies, while cutaneous toxicities were mostly reported in two studies lead within the first time-period. Pulmonary, gastrointestinal, and hepatic toxicities, showed a more heterogeneous distribution of ES over time.
UNASSIGNED: Our findings showed that the frequency of irAEs remained stable across the two calendar periods examined in our meta-analysis. This finding suggests that RW data might not be able to identify a potential learning curve in detection and management of irAEs.