Real-World Outcomes of Patients with Metastatic Non-Small Cell Lung Cancer Treated with Programmed Cell Death Protein 1 Inhibitors in the Year Following US Regulatory Approval
Real-World Outcomes of Patients with Metastatic Non-Small Cell Lung Cancer Treated with Programmed Cell Death Protein 1 Inhibitors in the Year Following US Regulatory Approval
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DOI：
10.1634/theoncologist.2018-0307
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发表时间：
2019-05-01
期刊：
影响因子：
5.8
通讯作者：
Abernethy, Amy P.
中科院分区：
文献类型：
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作者：
Khozin, Sean;Carson, Kenneth R.;Abernethy, Amy P.
背景来自癌症临床试验的证据具有很强的内部有效性，但很难推广到现实世界的患者群体。在这里，我们分析了转移性非小细胞肺癌(MNSCLC)患者在美国监管部门批准后的第一年接受程序化细胞死亡蛋白1(PD-1)抑制剂治疗的真实结果。材料与方法利用社区癌症护理诊所常规患者护理过程中收集的电子健康记录(EHR)数据进行回顾性研究。队列包括从2011年1月1日至2016年3月31日期间因转移疾病而接受nivolumab或pembrolizumab治疗的mNSCLC患者(n=1,344)，并接受>；1EHR记录的就诊。晚期疾病诊断和首次EHR结构化数据输入之间有90天间隔的患者被排除在外。结果中位生存期(OS)为8.0个月(95%可信区间为7.4~9.0个月)。估计间变性淋巴瘤激酶重排和表皮生长因子受体突变阳性肿瘤患者的中位OS为4.7个月(3.4-6.6)，而没有这种突变的患者为8.6个月(7.7-10.6)。PD-1抑制剂启动时的年龄或治疗路线不影响OS。结论这一分析表明，现实世界患者的OS可能比传统临床试验患者队列中的OS短，这可能是由于试验资格标准较窄。在免疫治疗开始时，不同治疗路线或年龄的OS没有差异，这表明PD-1抑制剂在多药治疗的mNSCLC患者中持续受益，年龄不是预后的预测因素。对患有合并症、器官功能障碍和多次既往治疗的患者的进一步研究正在进行中。对实践的影响这项研究评估了在监管部门批准后的一年内接受程序化细胞死亡蛋白1(PD-1)抑制剂治疗的转移性非小细胞肺癌患者的电子健康记录中的数据。与临床试验中报道的相比，这一真实世界队列中PD-1抑制剂启动的总生存期(OS)更短。晚期治疗不会影响OS，而且在免疫治疗开始时，75岁以上的患者的预后并不比年轻患者差。随着新疗法进入临床实践，真实世界的数据可以补充临床试验证据，提供有关推广的信息，并帮助为临床治疗决策提供信息。
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.