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Abstract：
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.
摘要：
免疫检查点抑制剂（ICIs）的监管批准是基于大的结果，随机临床试验，导致在此类试验中通常代表性不足的患者队列中结果数据有限.这项研究的目的是评估ICIs在这些独特的患者队列中的疗效和安全性。这是一个多中心,回顾性分析2011年1月1日至2018年4月1日美国6家学术和社区诊所的真实世界数据.如果患者接受了至少一个周期的ICI治疗，则将其包括在内。独特的患者队列包括年龄>75岁，非白人种族,吸烟史阳性,ECOG性能状态（PS）≥2，BMI≥30kg/m2，自身免疫性疾病（AIDs），慢性病毒感染（CVI），广泛的先验疗法(LOT)，或>三个转移部位。免疫相关不良事件（irAE），总生存期（OS），在整个队列和接受PD-（L）1单药治疗的NSCLC患者中评估治疗失败的时间。在单变量分析和多变量分析中，将结果及其与独特患者队列的关联与整个NSCLCPD-（L）1单一疗法队列中没有特定特征的那些进行了比较。总的来说,1453例患者包括：56.5%-吸烟者，30.4%-非白人，22.8%-老年人，20.8%-ECOGPS≥2，15.7%-艾滋病病史，4.7%-CVI历史。常见的ICIs是nivolumab（37.1%）和pembrolizumab（22.2%）。黑人患者,与白人患者相比，经历了较少的IRAE（OR0.54，p<0.001）。ECOGPS≥2（HR=2.01，p<0.001）和以前的LOT数量增加与不良OS相关（中位OS为26.2vs.16.2vs.一个vs.9.6个月两个vs.三个先前的房子，p<0.001)。上述结果在抗PD-(L)1单一疗法非小细胞肺癌患者(n=384)中得到证实。总的来说,在这些通常代表性不足的患者队列中，ICI是安全有效的。我们注意到ECOGPS≥2和先前LOT增加与ICI疗效差相关，黑人患者,与白人患者相比，经历了较少的IrAE。
