Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials
Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials
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DOI：
10.1001/jamaoncol.2018.0798
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发表时间：
2018-08-01
期刊：
影响因子：
28.4
通讯作者：
Gross, Cary P.
中科院分区：
文献类型：
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作者：
O'Connor, Jeremy M.;Fessele, Kristen L.;Gross, Cary P.
重要性 美国食品和药物管理局 (FDA) 正在加快批准新型癌症治疗药物的步伐，包括程序性细胞死亡 1 蛋白的免疫检查点抑制剂（抗 PD-1 药物）。然而，人们对抗 PD-1 药物在实践中到达符合条件的患者的速度有多快，或者这些患者是否与导致 FDA 批准的临床试验（关键临床试验）中研究的患者有所不同知之甚少。 目的 评估抗 PD-1 药物在实践中到达符合条件的患者的速度，并将临床实践中治疗的患者的年龄与关键临床试验中治疗的患者的年龄进行比较。 设计、设置和参与者 这项回顾性队列研究于 1 月 1 日开始进行， 2011 年至 2016 年 8 月 31 日，包括来自 Flatiron Health Network 的、有资格接受抗 PD-1 治疗的选定癌症类型的患者，其中包括黑色素瘤、非小细胞肺癌 (NSCLC) 和肾细胞癌 (RCC)。 主要结果和测量 接受抗 PD-1 治疗的合格患者的累计比例及其年龄分布。 结果 该研究确定了 3089 名符合接受抗 PD-1 治疗资格的患者。抗 PD-1 治疗（黑色素瘤患者的中位年龄为 66 [四分位间距，56-75] 岁，RCC 患者的中位年龄为 66 [四分位间距，58-72] 岁，NSCLC 患者的中位年龄为 67 [四分位间距，59-74] 岁；1742 名男性 [56.4%] 和 1347 名女性 [43.6%]；2066 [66.9%] 白色）。在这些患者中，2123例（68.7%）接受了抗PD-1治疗，其中439例符合条件的黑色素瘤患者（79.1%）、1417例符合条件的NSCLC患者（65.6%）和267例符合条件的RCC患者（71.2%）。 FDA 批准后 4 个月内，每个队列中超过 60% 的合格患者接受了抗 PD-1 治疗。总体而言，在 FDA 批准后的前 9 个月内，老年和年轻患者接受抗 PD-1 治疗的比例相似。然而，临床试验参与者和临床实践中接受抗 PD-1 治疗的患者之间的年龄存在显着差异，临床实践中年龄超过 65 岁的患者更多（范围：1365 名中的 327 名 [60.6%] 至 72 名中的 46 名 [63.9%]）比关键临床试验中年龄超过 65 岁的患者更多（范围：120 名中的 38 名 [31.7%] 至 544 名中的 223 名 [41.0%]；所有磷
IMPORTANCE The US Food and Drug Administration (FDA) is increasing its pace of approvals for novel cancer therapeutics, including for immune checkpoint inhibitors of programmed cell death 1 protein (anti-PD-1 agents). However, little is known about how quickly anti-PD-1 agents reach eligible patients in practice or whether such patients differ from those studied in clinical trials that lead to FDA approval (pivotal clinical trials).OBJECTIVES To assess the speed with which anti-PD-1 agents reached eligible patients in practice and to compare the ages of patients treated in clinical practice with the ages of those treated in pivotal clinical trials.DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study, performed from January 1, 2011, through August 31, 2016, included patients from the Flatiron Health Network who were eligible for anti-PD-1 treatment of selected cancer types, which included melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC).MAIN OUTCOMES AND MEASURES Cumulative proportions of eligible patients receiving anti-PD-1 treatment and their age distributions.RESULTS The study identified 3089 patients who were eligible for anti-PD-1 treatment (median age, 66 [interquartile range, 56-75] years for patients with melanoma, 66 [interquartile range, 58-72] years for patients with RCC, and 67 [interquartile range, 59-74] years for patients with NSCLC; 1742 male [56.4%] and 1347 [43.6%] female; 2066 [66.9%] white). Of these patients, 2123 (68.7%) received anti-PD-1 treatment, including 439 eligible patients with melanoma (79.1%), 1417 eligible patients with NSCLC (65.6%), and 267 eligible patients with RCC (71.2%). Within 4 months after FDA approval, greater than 60% of eligible patients in each cohort had received anti-PD-1 treatment. Overall, similar proportions of older and younger patients received anti-PD-1 treatment during the first 9 months after FDA approval. However, there were significant differences in age between clinical trial participants and patients receiving anti-PD-1 treatment in clinical practice, with more patients being older than 65 years in clinical practice (range, 327 of 1365 [60.6%] to 46 of 72 [63.9%]) than in pivotal clinical trials (range, 38 of 120 [31.7%] to 223 of 544 [41.0%]; all P