A Conceptual Framework For Cautious Escalation Of Anticancer Treatment: How To Optimize Overall Benefit And Obviate The Need For De-Escalation Trials

Cancer Treatment Reviews, Vol 0, No. 0, March 2024 (Forthcoming)

22 Pages Posted: 3 May 2023 Last revised: 8 Feb 2024

See all articles by Ivan Pourmir

Ivan Pourmir

Universite Paris Descartes - Assistance Publique - Hôpitaux de Paris

Hendrik Van Halteren

Admiraal De Ruyter Hospital

Reza Elaidi

Independent

Dario Trapani

European Institute of Oncology (IEO) IRCCS

Florian Strasser

University of Bern

Gerard Vreugdenhil

Maxima Medical Centre

Mike Clarke

Queen's University Belfast - Centre for Public Health

Date Written: April 21, 2023

Abstract

Background: The research designs used for current anticancer drug clinical development are often not suitable to determine an optimal efficacy threshold. This may lead to overtreatment, with potentially avoidable physical, emotional and financial toxicities. Also, it undermines the success rate of promising therapies, when dose is not optimized and dose-dependent toxicities are detrimental. Post-approval de-escalation trials that are then needed for dose-optimization and treatment de-intensification can require much more resources and time.

Design: Physicians and patient advocates were united in a special session on “De-escalation of treatment in Medical Oncology” at the European Society for Medical Oncology congress in 2022 to review issues of current trial designs as well as potential solutions. The supporting theoretical basis and practical examples from the literature were then compiled and summarized to propose a new framework for clinical trials in oncology.

Result: We provide the theoretical basis of a Framework for Cautious Escalation (FCE) of anticancer treatments, that aims to minimize overtreatment for a given level of benefit, but which may also increase the success rate of clinical trials. We use historical examples of cancer clinical trials to demonstrate how the application of FCE may have prevented potential overtreatments, optimized use of resources and obviated the need for subsequent de-escalation trials.

Conclusion: We propose the FCE as a new model of clinical development in oncology to prevent overtreatment and associated issues, to ultimately increase the success rate of clinical trials and deliver improved patient-centric outcomes.

Note:
Funding Information: None declared.

Conflict of Interests: The authors have declared no conflicts of interest.

Keywords: clinical trials, methodology, overtreatment, de-escalation

Suggested Citation

Pourmir, Ivan and Van Halteren, Hendrik and Elaidi, Reza and Trapani, Dario and Strasser, Florian and Vreugdenhil, Gerard and Clarke, Mike, A Conceptual Framework For Cautious Escalation Of Anticancer Treatment: How To Optimize Overall Benefit And Obviate The Need For De-Escalation Trials (April 21, 2023). Cancer Treatment Reviews, Vol 0, No. 0, March 2024 (Forthcoming), Available at SSRN: https://ssrn.com/abstract=4425584 or http://dx.doi.org/10.2139/ssrn.4425584

Ivan Pourmir (Contact Author)

Universite Paris Descartes - Assistance Publique - Hôpitaux de Paris ( email )

France

Hendrik Van Halteren

Admiraal De Ruyter Hospital

Reza Elaidi

Independent

Dario Trapani

European Institute of Oncology (IEO) IRCCS ( email )

Florian Strasser

University of Bern ( email )

Gerard Vreugdenhil

Maxima Medical Centre ( email )

Netherlands

Mike Clarke

Queen's University Belfast - Centre for Public Health ( email )

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
55
Abstract Views
258
Rank
750,004
PlumX Metrics