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Twitter: #Gettingthedoseright23

Background

Over the last two years, FDA and ASCO have cosponsored several workshops that have highlighted the limitations to our current strategies for determining the recommended dosage(s) of anticancer agents for evaluation in registration trials. Specifically, discussions at the 2021 workshop on Defining a Research Agenda to Address Barriers and Solutions to Oral Anticancer Agent Adherence found that a primary barrier to adherence is poor tolerability for patients at the recommended labeled dosage. In 2022, a workshop on Getting the Dose Right: Optimizing Dose Selection Strategies in Oncology explored the research and clinical challenges for dosage optimization for anticancer therapies administered as single agents. It concluded that oncology needs a paradigm shift to optimize dosage selection for  new drugs and highlighted strategies to achieve dosage optimization in the premarket setting. 

A primary challenge to dosage optimization in oncology is that dosage selection is often based on the maximum tolerated dosage or highest administered dosage, which was an approach developed for cytotoxic chemotherapies. In contrast, most anticancer agents currently in development are targeted therapies, many of which are oral drugs. Higher doses of targeted therapies may not have greater antitumor effects, and patients may stay on these therapies for long periods of time, increasing the importance of tolerability. Dosage optimization in oncology is further complicated by the use of anticancer drugs in combinations that have additive or potentially synergistic effects but also greater toxicity than when administered as monotherapies.

The FDA and American Society of Clinical Oncology (ASCO) have expressed a willingness to leverage their combined strengths for the joint development of the substantive actions of a workshop related to optimizing dosage selection in combination therapies.  Specific topics to discuss at this workshop could include: 

• Determining the challenges to dosage optimization for combination therapies 
• Identifying nonclinical data that support dosage optimization of the combination therapy
• Assessing pharmacokinetic and pharmacodynamic interactions for dosage optimization of combination regimens
• Evaluating trial designs to support dosage optimization of combination therapies 

The workshop will include four sessions and will be fully virtual and open to the public. Meeting registration is required using the link provided above.

Meeting Goals

• Provide a forum for open discussion among academia, industry, regulatory agencies, and patient groups about optimizing the dosage of combination anticancer agents. 
• Discuss how to apply nonclinical, clinical pharmacology, clinical, and statistical evaluations to optimize the dosages of combination anticancer agents.
• Discuss benefits and challenges related to pre- marketing dosage optimization trials of combination agents.
• Discuss clinician and patient factors that impact participation in pre- marketing dosage optimization trials of combination agents.

Workshop Materials

• Agenda 
• Biographies
  • Day 1
  • Day 2
• Day 1 Recording 
• Day 2 Recording 

Contacts

Caitlin Drew, MSN, RN
Senior Regulatory Health Project Manager
Oncology Center of Excellence, (OCE)
Office of the Commissioner (OC)
U.S. Food and Drug Administration
10903 New Hampshire Ave, Silver Spring, MD 20993
Tel: 301.318.8609
Caitlin.Drew@fda.hhs.gov

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