Dose-finding designs for trials of molecularly targeted agents and immunotherapies

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  • Chiuzan, Cody
    • Other Affiliation: Department of Biostatistics; Mailman School of Public Health; Columbia University
  • Shtaynberger, Jonathan
    • Other Affiliation: Department of Biostatistics; Mailman School of Public Health; Columbia University
  • Manji, Gulam A.
    • Other Affiliation: Division of Hematology and Oncology; Department of Medicine; Columbia University
  • Duong, Jimmy K.
    • Other Affiliation: Department of Biostatistics; Mailman School of Public Health; Columbia University
  • Schwartz, Gary K.
    • ORCID: 0000-0003-1813-5061
    • Other Affiliation: Division of Hematology and Oncology; Department of Medicine; Columbia University
  • Ivanova, Anastasia
    • Gillings School of Global Public Health, Department of Biostatistics
  • Lee, Shing M.
    • Other Affiliation: Department of Biostatistics; Mailman School of Public Health; Columbia University
Abstract
  • Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, only 7.1% of trials use novel designs.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Journal of Biopharmaceutical Statistics
Journal volume
  • 27
Journal issue
  • 3
Page start
  • 477
Page end
  • 494
Language
  • English
ISSN
  • 1520-5711
  • 1054-3406

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