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

JAMA Oncol. 2018 Aug 1;4(8):e180798. doi: 10.1001/jamaoncol.2018.0798. Epub 2018 Aug 9.


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 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 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 agents 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 agents treatment and their age distributions.

Results: The study identified 3089 patients who were eligible for anti-PD-1 agents 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 agents 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 agents treatment. Overall, similar proportions of older and younger patients received anti-PD-1 agents 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 agents 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 < .001).

Conclusions and relevance: Anti-PD-1 agents rapidly reached patients in clinical practice, and patients treated in clinical practice differed significantly from patients treated in pivotal clinical trials. Future actions are needed to ensure that rapid adoption occurs on the basis of representative trial evidence.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Clinical Trials as Topic*
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / pathology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nivolumab / therapeutic use*
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Retrospective Studies


  • Antibodies, Monoclonal, Humanized
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • pembrolizumab