Tolerability & Dosing
A critical part of defining the value of a new therapy is evaluating safety and efficacy. As targeted therapies have emerged and are used for longer periods of time, understanding the tolerability of a therapy and identifying the optimal dosage have become critical components of drug development. Friends of Cancer Research (Friends) worked with stakeholders to propose a definition of tolerability that includes the patient perspective:
“The tolerability of a medical product is the degree to which symptomatic and non-symptomatic adverse events associated with the product’s administration affect the ability or desire of the patient to adhere to the dose or intensity of therapy. A complete understanding of tolerability should include direct measurement from the patient on how they are feeling and functioning while on treatment.”
Friends work in this space focuses on key considerations for dosage-finding studies that include an understanding of tolerability.
What is the unmet need and why does it matter?
Selecting the optimal dosage requires a robust understanding of a therapy’s efficacy, safety, and tolerability. Traditionally, early-phase dosing trials aimed to identify the maximum tolerated dose (MTD), an approach designed for cytotoxic chemotherapies where an increase in dose leads to increased tumor suppression. In contrast, newer targeted therapies and immunotherapies may not require dosing at the MTD for maximal efficacy, and a lower dose may provide similar efficacy with an improved safety and tolerability profile for patients.
Recent initiatives from the U.S. Food and Drug Administration (FDA) Oncology Center of Excellence (OCE), like Project Optimus and guidance documents, indicate a desire for improved optimization in early phase development of oncology drugs and signal a need for renewed approaches to early phase dosing strategies. New strategies and tools are needed to support the timely identification of the optimal dose, including approaches for evaluating and comparing tolerability across dosages.
How are we helping to find solutions?
Since 2013, Friends has convened stakeholders across government, academia, advocacy, and industry to discuss strategies for optimizing the dosing of oncology drugs, including incorporating the patient voice into assessment of tolerability. See the timeline below to review details of the steps Friends has taken to find solutions.
How does this impact patients?
Optimizing drug dosages is crucial to minimizing adverse effects while maximizing therapeutic effectiveness. Achieving this balance not only enhances treatment efficacy, but also improves patient safety and quality of life, ultimately leading to the best possible clinical outcomes.
Project Outcomes
Friends prioritizes sharing findings from our projects with the public to inform policy:
White Papers
Friends Public Meetings
In October 2021, Friends Annual Meeting featured a panel discussion focused on current challenges to the implementation of dosage-finding studies in oncology, opportunities to improve dosing strategies given these ongoing challenges, and key considerations for selecting appropriate dosage optimization strategies in oncology.
In September 2021, Friends hosted a meeting to identify opportunities to optimize the Breakthrough Therapy designation, which led to the development of a dosing “snapshot” document. This tool facilitates early conversations between FDA and sponsors on dosing strategies.
In October 2015, Friends Annual Meeting featured a panel discussion and white paper on, “Capturing Symptomatic Adverse Events from the Patients’ Perspective: The Potential Role of the National Cancer Institute’s PRO-CTCAE Measurement System.”
In October 2013, Friends Annual Meeting featured a panel discussion and white paper on “Optimizing Dosing of Oncology Drugs.” The white paper identified the challenges of optimizing the dosing of oncology drugs and described potential solutions to improve dosing and administration guidance for health care professionals.