Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Acta Oncol. 2022 Apr;61(4):409-416. doi: 10.1080/0284186X.2021.2023213. Epub 2022 Jan 11.
Immune checkpoint inhibitors (ICIs) are implemented as standard treatment for patients with advanced non-small cell lung cancer (NSCLC) in first-line and subsequent-line treatment. However, certain subgroups such as patients with older age, poor performance status (PS), and severe comorbidity are underrepresented in the randomized controlled trials (RCTs). This study aimed to assess overall survival (OS), treatment data, and clinical features affecting second- or subsequent-line ICI efficacy in an unselected, Danish, nationwide NSCLC population.
Patients with advanced NSCLC who started nivolumab or pembrolizumab as second-line or subsequent-line treatment between 1 September 2015, and 1 October 2018, were identified from institutional records of all Danish oncology departments. Clinical and treatment data were retrospectively collected. Descriptive statistics and survival analyses were performed.
Data were available for 840 patients; 49% females. The median age was 68 years (19% were ≥75 years), 19% had PS ≥2, and 36% had moderate to severe comorbidity. The median OS (mOS) was 12.2 months; 15.1 months and 10.0 months in females and males, respectively. The median time-to-treatment discontinuation (mTTD) and median progression-free survival (mPFS) was 3.2 and 5.2 months, respectively. Patients with PS ≥2 had a mOS of 4.5 months, mTTD of 1.1 month, and mPFS of 2.0 months. In multivariable Cox regression analysis, male sex (HR = 1.35, 95% CI 1.11-1.62), PS >0 (PS 1, HR = 1.88, 95% CI 1.52-2.33; PS ≥2, HR = 4.15, 95% CI 3.13-5.5), liver metastases (HR = 1.72, 95% CI 1.34-2.22), and bone metastases (HR = 1.27, 95% CI 1.03-1.58) were significant poor prognostic OS factors.
Danish real-world patients with advanced NSCLC treated with second- or subsequent-line ICI had an OS comparable to results from RCTs. Women, frail and older patients constituted a higher proportion than in previous RCTs. Clinical features associated with poor OS were male sex, PS ≥1 (in particular PS ≥2), bone-, and liver metastases.
免疫检查点抑制剂（ICIs）已被用作晚期非小细胞肺癌（NSCLC）患者一线和后续治疗的标准治疗方法。然而，在随机对照试验（RCT）中，某些亚组（如年龄较大、表现状态较差[PS]和严重合并症的患者）代表性不足。本研究旨在评估在未经选择的丹麦全国性 NSCLC 人群中，二线或后续 ICI 疗效的总生存期（OS）、治疗数据和影响临床特征。
从所有丹麦肿瘤学部门的机构记录中确定了 2015 年 9 月 1 日至 2018 年 10 月 1 日期间开始二线或后续 nivolumab 或 pembrolizumab 治疗的晚期 NSCLC 患者。回顾性收集临床和治疗数据。进行描述性统计和生存分析。
共 840 例患者的数据可用；女性占 49%。中位年龄为 68 岁（19%≥75 岁），19%的 PS≥2，36%的患者有中度至重度合并症。中位 OS（mOS）为 12.2 个月；女性和男性分别为 15.1 个月和 10.0 个月。中位治疗停药时间（mTTD）和中位无进展生存期（mPFS）分别为 3.2 个月和 5.2 个月。PS≥2 的患者的 mOS 为 4.5 个月，mTTD 为 1.1 个月，mPFS 为 2.0 个月。多变量 Cox 回归分析显示，男性（HR=1.35，95%CI 1.11-1.62）、PS>0（PS1，HR=1.88，95%CI 1.52-2.33；PS≥2，HR=4.15，95%CI 3.13-5.5）、肝转移（HR=1.72，95%CI 1.34-2.22）和骨转移（HR=1.27，95%CI 1.03-1.58）是 OS 的不良预后因素。
丹麦真实世界中接受二线或后续 ICI 治疗的晚期 NSCLC 患者的 OS 与 RCT 结果相当。女性、虚弱和老年患者的比例高于以往的 RCT。与 OS 不良相关的临床特征是男性、PS≥1（尤其是 PS≥2）、骨和肝转移。
