Dose Finding of Small-Molecule Oncology Drugs: Optimization throughout the Development Life Cycle

Area of Science:

• Oncology drug development
• Pharmacokinetics and pharmacodynamics
• Clinical trial design

Background:

• Rapid marketing approvals for oncology drugs necessitate continuous dose finding and optimization.
• Many oncology drug trials experience high rates of dose reductions and discontinuations, leading to postmarketing requirements (PMRs).
• Kinase inhibitors are particularly prone to these issues, with eight of 31 approved drugs having PMRs.

Discussion:

• The current paradigm for oncology drug dose finding and optimization requires improvement.
• Traditional 3+3 designs may not be optimal; newer strategies should be considered.
• Dose optimization should extend beyond Phase I and continue throughout drug development.

Key Insights:

• High rates of dose modifications in oncology trials impact regulatory approval.
• Postmarketing requirements for alternate doses are common, especially for kinase inhibitors.
• Improved dose-finding strategies are essential for timely and appropriate drug approval.

Outlook:

• Implementing newer dose-finding strategies can enhance the precision of dosing.
• Continued dose optimization throughout development increases the probability of achieving the right dose.
• This approach aims to ensure the right drug is given at the right dose for optimal patient outcomes.