Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%—smokers, 30.4%—non-White, 22.8%—elderly, 20.8%—ECOG PS ≥ 2, 15.7%—history of AIDs, and 4.7%—history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54,p< 0.001). An ECOG PS of ≥2 (HR = 2.01,p< 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs,p< 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.
免疫检查点抑制剂（ICIs）的监管批准基于大型随机临床试验的结果，导致在此类试验中通常代表性不足的患者群体疗效数据有限。本研究旨在评估ICIs在这些特殊患者群体中的疗效与安全性。这是一项多中心回顾性真实世界数据分析，涵盖2011年1月1日至2018年4月1日期间美国六家学术及社区诊所的数据。纳入标准为至少接受过一个周期ICI治疗的患者。特殊患者群体包括：年龄>75岁、非白人族裔、有吸烟史、ECOG体能状态（PS）≥2、体重指数（BMI）≥30 kg/m²、患有自身免疫性疾病（AIDs）、慢性病毒感染（CVI）、既往接受过多线治疗（LOTs）或存在超过三个转移部位。研究评估了整体队列及接受PD-(L)1单药治疗的非小细胞肺癌（NSCLC）患者的免疫相关不良事件（irAEs）、总生存期（OS）和治疗失败时间。通过单变量和多变量分析，将特殊患者群体的结局与其在整体NSCLC PD-(L)1单药治疗队列中无相应特征的患者进行比较。共纳入1453例患者：56.5%有吸烟史，30.4%为非白人族裔，22.8%为高龄患者（>75岁），20.8% ECOG PS≥2，15.7%有AIDs病史，4.7%有CVI病史。常用ICIs为纳武利尤单抗（37.1%）和帕博利珠单抗（22.2%）。与白人患者相比，黑人患者irAEs发生率较低（OR 0.54，p<0.001）。ECOG PS≥2（HR=2.01，p<0.001）以及既往LOTs增加与较差的OS相关（既往接受一线、二线、三线治疗患者的中位OS分别为26.2个月、16.2个月和9.6个月，p<0.001）。上述结果在抗PD-(L)1单药治疗的NSCLC患者（n=384）中得到验证。总体而言，ICIs在这些通常代表性不足的患者群体中安全有效。我们注意到ECOG PS≥2和既往LOTs增加与ICI疗效较差相关，且与白人患者相比，黑人患者irAEs发生率更低。
肿瘤(癌症)患者之家