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Sequential, Multiple Assignment, Randomized Trial Designs in Immuno-oncology Research

Kelley M Kidwell1, Michael A Postow2,3, Katherine S Panageas4

  • 1Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, Michigan. kidwell@umich.edu.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|August 25, 2017
PubMed

Insights

Sequential, multiple assignment, randomized trial (SMART) designs offer a novel approach to optimizing cancer immunotherapy. This adaptive trial method aims to identify the most effective immune checkpoint inhibitor regimens for longer survival and reduced toxicity.

Area of Science:

  • Immunology and Oncology
  • Clinical Trial Design

Background:

  • Immune checkpoint inhibitors (ICIs) like anti-CTLA-4, anti-PD-1, and anti-PD-L1 are FDA-approved for various cancers.
  • Combination immunotherapy shows higher efficacy than single agents in metastatic melanoma but increases toxicity.
  • Optimal initial therapy and dosing strategies for ICIs remain under investigation.

Purpose of the Study:

  • To introduce and evaluate the Sequential, Multiple Assignment, Randomized Trial (SMART) design for optimizing cancer immunotherapy.
  • To demonstrate how SMART designs can identify adaptive treatment regimens based on individual patient response.
  • To compare the efficiency and benefits of SMART designs against traditional randomized clinical trials.

Main Methods:

  • Description of the SMART design methodology for evaluating immune checkpoint inhibitors.
  • Presentation of a hypothetical SMART design for BRAF wild-type metastatic melanoma.
  • Comparative analysis of SMART designs versus multiple traditional randomized trials.

Main Results:

  • SMART designs allow for adaptive treatment allocation within individuals based on intermediate response.
  • Illustrates the potential benefits of SMART designs over traditional trial structures.
  • Acknowledges the inherent complexity in implementing SMART designs.

Conclusions:

  • SMART designs represent an optimal strategy for discovering immunotherapy regimens that maximize durable response and survival.
  • This adaptive approach may lead to improved patient outcomes with potentially lower toxicity.
  • Further exploration of SMART designs is warranted for advancing cancer immunotherapy research.

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