Confounding factors in exposure-response analyses and mitigation strategies for monoclonal antibodies in oncology.
Br J Clin Pharmacol
; 87(6): 2493-2501, 2021 06.
Article
in En
| MEDLINE
| ID: mdl-33217012
ABSTRACT
Dose selection and optimization is an important topic in drug development to maximize treatment benefits for all patients. While exposure-response (E-R) analysis is a useful method to inform dose-selection strategy, in oncology, special considerations for prognostic factors are needed due to their potential to confound the E-R analysis for monoclonal antibodies. The current review focuses on 3 different approaches to mitigate the confounding effects for monoclonal antibodies in oncology (i) Cox-proportional hazards modelling and case-matching; (ii) tumour growth inhibition-overall survival modelling; and (iii) multiple dose level study design. In the presence of confounding effects, studying multiple dose levels may be required to reveal the true E-R relationship. However, it is impractical for pivotal trials in oncology drug development programmes. Therefore, the strengths and weaknesses of the other 2 approaches are considered, and the favourable utility of tumour growth inhibition-overall survival modelling to address confounding in E-R analyses is described. In the broader scope of oncology drug development, this review discusses the downfall of the current emphasis on E-R analyses using data from single dose level trials and proposes that development programmes be designed to study more dose levels in earlier trials.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Agents, Immunological
/
Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Br J Clin Pharmacol
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos