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

Cody Chiuzan, Jonathan Shtaynberger, Gulam A. Manji, Jimmy K. Duong, Gary K. Schwartz, Anastasia Ivanova, Shing M. Lee

Research output: Contribution to journalArticle

  • 1 Citations

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, the adoption of these designs continues to remain low.

LanguageEnglish (US)
Pages477-494
Number of pages18
JournalJournal of Biopharmaceutical Statistics
Volume27
Issue number3
DOIs
StatePublished - May 4 2017

Fingerprint

Immunotherapy
Dose Finding
Toxicity
Drug Design
Radiotherapy
Drug Therapy
Therapy
Therapeutics
Model-based
Design
Oncology
Surge
Chemotherapy
Percentage
Efficacy
Drugs
Continue
Inclusion
Flexibility
Specification

Keywords

  • Dose-finding methods
  • immunotherapy
  • maximum tolerated dose
  • optimal dose
  • phase 1 designs
  • targeted therapy

ASJC Scopus subject areas

  • Statistics and Probability
  • Pharmacology
  • Pharmacology (medical)

Cite this

Chiuzan, C., Shtaynberger, J., Manji, G. A., Duong, J. K., Schwartz, G. K., Ivanova, A., & Lee, S. M. (2017). Dose-finding designs for trials of molecularly targeted agents and immunotherapies. Journal of Biopharmaceutical Statistics, 27(3), 477-494. DOI: 10.1080/10543406.2017.1289952

Dose-finding designs for trials of molecularly targeted agents and immunotherapies. / Chiuzan, Cody; Shtaynberger, Jonathan; Manji, Gulam A.; Duong, Jimmy K.; Schwartz, Gary K.; Ivanova, Anastasia; Lee, Shing M.

In: Journal of Biopharmaceutical Statistics, Vol. 27, No. 3, 04.05.2017, p. 477-494.

Research output: Contribution to journalArticle

Chiuzan, C, Shtaynberger, J, Manji, GA, Duong, JK, Schwartz, GK, Ivanova, A & Lee, SM 2017, 'Dose-finding designs for trials of molecularly targeted agents and immunotherapies' Journal of Biopharmaceutical Statistics, vol 27, no. 3, pp. 477-494. DOI: 10.1080/10543406.2017.1289952
Chiuzan C, Shtaynberger J, Manji GA, Duong JK, Schwartz GK, Ivanova A et al. Dose-finding designs for trials of molecularly targeted agents and immunotherapies. Journal of Biopharmaceutical Statistics. 2017 May 4;27(3):477-494. Available from, DOI: 10.1080/10543406.2017.1289952
Chiuzan, Cody ; Shtaynberger, Jonathan ; Manji, Gulam A. ; Duong, Jimmy K. ; Schwartz, Gary K. ; Ivanova, Anastasia ; Lee, Shing M./ Dose-finding designs for trials of molecularly targeted agents and immunotherapies. In: Journal of Biopharmaceutical Statistics. 2017 ; Vol. 27, No. 3. pp. 477-494
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