Some statistical considerations in the clinical development of cancer immunotherapies

Pharmaceutical Statistics
Bo Huang

Abstract

Immuno-oncology has emerged as an exciting new approach to cancer treatment. Common immunotherapy approaches include cancer vaccine, effector cell therapy, and T-cell-stimulating antibody. Checkpoint inhibitors such as cytotoxic T lymphocyte-associated antigen 4 and programmed death-1/L1 antagonists have shown promising results in multiple indications in solid tumors and hematology. However, the mechanisms of action of these novel drugs pose unique statistical challenges in the accurate evaluation of clinical safety and efficacy, including late-onset toxicity, dose optimization, evaluation of combination agents, pseudoprogression, and delayed and lasting clinical activity. Traditional statistical methods may not be the most accurate or efficient. It is highly desirable to develop the most suitable statistical methodologies and tools to efficiently investigate cancer immunotherapies. In this paper, we summarize these issues and discuss alternative methods to meet the challenges in the clinical development of these novel agents. For safety evaluation and dose-finding trials, we recommend the use of a time-to-event model-based design to handle late toxicities, a simple 3-step procedure for dose optimization, and flexible rule-base...Continue Reading

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Citations

Oct 20, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Apostolia M TsimberidouMichael A Postow
Oct 21, 2018·Journal for Immunotherapy of Cancer·Apostolia M TsimberidouMichael A Postow
Sep 10, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Meredith M ReganDavid F McDermott
Aug 28, 2019·Clinical Trials : Journal of the Society for Clinical Trials·Xiaodong LuoHui Quan
Nov 2, 2019·Pharmaceutical Statistics·Gaohong DongDavid C Hoaglin
Jun 27, 2020·Journal of Biopharmaceutical Statistics·Guanghan Frank Liu, Jason J Z Liao
Aug 10, 2019·World Journal of Clinical Oncology·Mona PasslerKlaus Pietzner
Aug 9, 2020·Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research·Anna WikstenSandro Gsteiger

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