OBJECTIVE Phase III studies of checkpoint inhibitors changed the therapeutic landscape for lung cancer. In 2015 the Dutch Society of Chest Physicians (NVALT) introduced a national immunotherapy registry for patients with lung cancer; quality standards for hospitals were implemented. At population level we studied clinical benefit in daily practice and in patients who are underrepresented in phase III trials. MATERIALS AND METHODS From the initial introduction of checkpoint inhibitors in the Netherlands patients were centrally registered. Educational programs and quality control were provided under supervision of NVALT. The largest immunotherapy providing hospitals were compared to hospitals who provided less checkpoint inhibitors as marker of experience. Patients characteristics, treatment and side effects, response rate and survival were studied. RESULTS A total of 2676 patients were registered, 2302 with follow up data were evaluated. Between October 2015 and December 2017 a gradual increase from 12 to 30 qualified hospitals showed no major toxicity differences. Toxicity led to a hospital admission rate of 9.1 with an average duration of 10.4 days. Overall tumor response was 21.8 % and median overall survival 12.6 months. Overall survival was not significantly different for patients aged ≥ 75 years, those having brain metastases or selected auto-immune diseases before start checkpoint inhibitors compared to younger patients or those without, respectively. Survival outcomes were worse in patients with PS 2+, non-smokers, and patients who received any palliative radiotherapy (HR 2.1, 95 % CI 1.7-2.7; 1.3, 95 % CI 1.0-1.6 and 1.2, 95 % CI 1.1-1.4, respectively). CONCLUSIONS Changes in the therapeutic landscape did not lead to major differences in quality of care between hospitals. Elderly patients, those with brain metastases or selected auto-immune disease underrepresented in clinical trials did not do worse on checkpoint inhibitors, except for those with PS 2 + .

中文翻译：

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美国国家免疫治疗注册中心的人口水平上检查点抑制剂对晚期非小细胞肺癌的影响。

目的III期检查点抑制剂的研究改变了肺癌的治疗前景。2015年，荷兰胸科医师协会（NVALT）推出了针对肺癌患者的国家免疫疗法注册机构；医院质量标准得到执行。在人群水平上，我们研究了在日常实践中以及在III期临床研究中代表性不足的患者的临床获益。材料和方法从最初在荷兰引入检查点抑制剂开始，就对患者进行了集中登记。在NVALT的监督下提供了教育计划和质量控制。将提供最大免疫疗法的医院与提供较少检查点抑制剂作为经验指标的医院进行比较。研究了患者的特征，治疗和副作用，缓解率和生存率。结果共登记了2676例患者，对2302例患者进行了随访数据评估。在2015年10月至2017年12月期间，合格的医院从12家逐步增加到30家，显示无重大毒性差异。毒性导致入院率为9.1，平均住院时间为10.4天。总体肿瘤反应率为21.8％，中位总生存期为12.6个月。≥75岁的患者，开始转移检查点抑制剂之前有脑转移或选择的自身免疫性疾病的患者的总生存率与年轻患者或无此疾病的患者相比无显着差异。PS 2+，非吸烟者和接受姑息放疗的患者的生存结局更差（HR 2.1，95％CI 1.7-2.7; 1.3，95％CI 1.0-1.6和1.2，95％CI 1.1-1.4 ， 分别）。结论治疗环境的变化并未导致医院之间的护理质量出现重大差异。老年患者，脑转移瘤或某些自身免疫性疾病在临床试验中表现不足的患者，除PS 2 +者外，对检查点抑制剂的治疗没有恶化。