Efficacy gap between phase II and subsequent phase III studies in oncology
Rick A Vreman1,2, Svetlana V Belitser1, Ana T M Mota1
1Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands.
British Journal of Clinical Pharmacology
|February 9, 2020
Summary
Clinical trial efficacy in oncology shows minimal average differences between phase II and phase III trials. However, substantial variability exists, underscoring the need for robust study design and evidence evaluation.
Area of Science:
- Oncology Clinical Trials
- Drug Development
- Regulatory Science
Background:
- Increasing flexibility in evidence generation timing relative to marketing authorization.
- Option to conduct Phase III trials post-authorization or omit them entirely.
Purpose of the Study:
- Investigate the relationship between Phase II and Phase III clinical trial efficacy in oncology.
- Analyze the consistency of efficacy endpoints across trial phases.
Main Methods:
- Included European Medicines Agency-approved oncology drugs (2007-2016).
- Matched Phase II and III trials by indication, treatment, and patient characteristics.
- Analyzed objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) using weighted mixed-effects regression.
Main Results:
- Identified 81 Phase II-III matches (252 trials).
- Found minimal average differences: -4.2% for ORR, 2.1 months for PFS, -0.3 months for OS.
- Observed substantial variability in differences across indications for all outcomes.
Conclusions:
- Lack of significant average differences suggests focusing on overall evidence quality over trial phase.
- High variability highlights the critical need for replication to confirm oncology drug efficacy.
- Identifying factors influencing demonstrated effects remains essential.
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