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FDA Workshop: Opportunities to Improve Dose Optimization: Designing Trials and Applying Pharmacometrics

*May 2022*

EGFR Resisters co-founder Jill Feldman participated as a panelist in this FDA Oncology Workship:  3a “Opportunities to Improve Dose Optimization: Designing Trials and Applying Pharmacometrics; and 3b “Opportunities to Improve Dose Optimization: Assessing Safety and Tolerability.”

Current strategies for determining the recommended dose(s) of anticancer agents for evaluation in registration trials are often outdated and based on a historical drug development paradigm developed for cytotoxic chemotherapies. For cytotoxic chemotherapies, higher doses of the drug were thought to have greater antitumor activity. Dose selection was based on exposing small groups of patients to increasing doses and observing them for life-threatening toxicities to determine the maximum tolerated dose. Patients typically received cytotoxic chemotherapies for a short period of time. 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. New approaches to optimize doses of targeted anticancer agents are needed.

In February 2021, American Society of Clinical Oncology (ASCO) and the U.S. Food and Drug Administration (FDA) cosponsored a workshop on oral adherence. A primary barrier to adherence identified was that labeled doses may be higher than necessary to achieve efficacy and have poor tolerability for patients. A strategy identified to improve adherence was to pursue dose optimization strategies that maintain efficacy while minimizing toxicity.

In this follow-on workshop, the FDA and ASCO will discuss research and clinical challenges for dose optimization and highlight strategies to improve dose optimization for anticancer agents. Watch here.