Real-World Outcomes of Patients with Metastatic Non-Small Cell Lung Cancer Treated with Programmed Cell Death Protein 1 Inhibitors in the Year Following U.S. Regulatory Approval

Oncologist. 2019 May;24(5):648-656. doi: 10.1634/theoncologist.2018-0307. Epub 2018 Dec 27.


Background: Evidence from cancer clinical trials has strong internal validity but can be difficult to generalize to real-world patient populations. Here we analyzed real-world outcomes of patients with metastatic non-small cell lung cancer (mNSCLC) treated with programmed cell death protein 1 (PD-1) inhibitors in the first year following U.S. regulatory approval.

Materials and methods: This retrospective study leveraged electronic health record (EHR) data collected during routine patient care in community cancer care clinics. The cohort included patients with mNSCLC who had received nivolumab or pembrolizumab for metastatic disease (n = 1,344) with >1 EHR-documented visit from January 1, 2011, to March 31, 2016. Patients with a > 90-day gap between advanced disease diagnosis and first EHR structured data entry were excluded.

Results: Estimated median overall survival (OS) was 8.0 months (95% confidence interval 7.4-9.0 months). Estimated median OS was 4.7 months (3.4-6.6) for patients with anaplastic lymphoma kinase rearrangement- and epidermal growth factor receptor mutation-positive tumors, and 8.6 months (7.7-10.6) for patients without such mutations. Age at PD-1 inhibitor initiation or line of therapy did not impact OS.

Conclusion: This analysis suggests OS in real-world patients may be shorter than in conventional clinical trial patient cohorts, potentially due to narrow trial eligibility criteria. The lack of difference in OS by line of therapy or age at immunotherapy initiation suggests sustained benefit of PD-1 inhibitors in multitreated patients with mNSCLC and that age is not a predictor of outcome. Further studies are underway in patients with comorbidities, organ dysfunction, and multiple prior therapies.

Implications for practice: This study evaluated data derived from electronic health records of patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 (PD-1) inhibitors in the year following regulatory approval. This real-world cohort had shorter overall survival (OS) indexed to PD-1 inhibitor initiation than reported in clinical trials. Late-line treatment did not influence OS, and patients aged >75 at immunotherapy initiation did not have worse outcomes than younger patients. As new therapies enter clinical practice, real-world data can complement clinical trial evidence providing information on generalizability and helping inform clinical treatment decisions.


背景。虽然来自癌症临床试验的证据具有很强的内部效度,但是,人们可能很难将其推广到真实世界的患者群体中。在本研究中,我们对在美国监管机构批准后第一年将程序性细胞死亡蛋白 1 (PD‐1) 抑制剂用于治疗转移性非小细胞肺癌 (mNSCLC) 患者的真实世界结果进行分析。

材料和方法。本回顾性研究利用在社区癌症治疗诊所的常规患者治疗期间收集的电子病历 (EHR) 数据。队列包含曾接受针对转移性疾病的纳武单抗和帕博利珠单抗治疗的 mNSCLC 患者 (n = 1 344),他们在 2011 年 1 月 1 日至 2016 年 3 月 31 日期间已完成 >1 次 EHR 记录的看诊。我们已排除晚期疾病诊断与首次 EHR 结构化数据录入之间的时间跨度 > 90 天的患者。

结果。预估的中位总生存期 (OS) 为 8.0 个月(95% 置信区间 7.4–9.0 个月)。在出现间变性淋巴瘤激酶重排阳性和表皮生长因子受体突变阳性的患者中,预估的中位 OS 为 4.7 个月 (3.4–6.6);在未出现此类突变的患者中,预估的中位 OS 为 8.6 个月 (7.7–10.6)。开始 PD‐1 抑制剂治疗的年龄或治疗线数不会影响 OS。

结论。本分析表明,真实患者的 OS 可能比传统临床试验患者队列的 OS 短,这可能是因为试验资格标准范围受限。按治疗线数或开始免疫治疗的年龄划分的 OS 之间没有差异,这表明 PD‐1 抑制剂可令经过多次治疗的 mNSCLC 患者持续获益,而且,年龄不是预后的预测因子。我们正在对既往曾经过多次治疗且患有并存病和器官功能障碍的患者实施进一步研究。

实践意义:本研究评估了在监管机构批准后第一年接受程序性细胞死亡蛋白 1 (PD‐1) 抑制剂治疗的转移性非小细胞肺癌患者的电子病历的数据。与临床试验报告的数据相比,此真实队列中与开始 PD‐1 抑制剂治疗相关的总生存期 (OS) 更短。后线治疗不会影响 OS;在开始免疫治疗时,年龄 >75 岁的患者不会比年轻患者取得更差的结果。


Keywords: Electronic health records; Nivolumab; Non‐small cell lung cancer; Overall survival; Pembrolizumab; Real‐world evidence.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Survival Analysis
  • United States


  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor