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Original Investigation
August 9, 2018

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

Author Affiliations
  • 1Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
  • 2National Clinician Scholars Program, Yale University School of Medicine, New Haven, Connecticut
  • 3Flatiron Health Inc, New York, New York
  • 4Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
  • 5The Ohio State University Comprehensive Cancer Center, Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus
JAMA Oncol. 2018;4(8):e180798. doi:10.1001/jamaoncol.2018.0798
Key Points

Question  How quickly have immune checkpoint inhibitors changed clinical practice?

Findings  In this cohort study of 3089 patients, most eligible patients were being treated with inhibitors of programmed cell death 1 protein within 4 months after US Food and Drug Administration approval, with treated patients being significantly older than those studied in the pivotal clinical trials that supported US Food and Drug Administration–approved use.

Meaning  Immune checkpoint inhibitors may have rapidly changed clinical practice among populations of patients who differ substantially from those studied in pivotal clinical trials.

Abstract

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.

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