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# Oncology Drug Dose Optimization Often Deferred: Analysis
- URL: https://www.fdaweb.com/oncology-drug-dose-optimization-often-deferred-analysis/
- Published: 2023-12-12T12:00:00.000Z
- Updated: 2026-09-14T14:18:21.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5155978

A new analysis by Friends of Cancer Research (FOCR) finds that more than half of all oncology drugs approved by FDA in the last decade had a postmarketing requirement (PMR) to obtain better dosing (optimal dose) information.

“Traditionally, early-phase oncology clinical trials aimed to identify the maximum tolerated dose (MTD), a dose optimization strategy designed for cytotoxic chemotherapies with which increasing the dose is associated with increasing efficacy,” the [analysis says](https://watermark.silverchair.com/ccr-23-2268.pdf?token=AQECAHi208BE49Ooan9kkhW%5FErcy7Dm3ZL%5F9Cf3qfKAc485ysgAAA3AwggNsBgkqhkiG9w0BBwagggNdMIIDWQIBADCCA1IGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMtWx2yzO91gN7I277AgEQgIIDI0lCyB2i7%5FUWPnAhpmhjiLIWJNG6SB8sh6wxqccgcsWGnUtxXIIzfvKUS92OpJ3ln3x7w5PYYw1ub7j0GPs5y4C0Jss0IVFG44Wu55XuxFuBdDpyfY8WHebL3O6aQylMnCXPyU4tqlyD5OMj5-czgdNNL0ngCcnk-d%5FbfPSoFEceW-spRyLTqRVGjWpOh8GbQHCWcuqXUGCKu7rgTIT75mQI7k7J6JOj8SQeLURUd81-pKuLev3crYX5Rw1VO1z-fNAiBuZ6k8ZXtLkIvBBZqGZ11LC-AWGbdzP09aTgNK4x-x0YPqE16G7FfeCa4GodmQxC6gS5sV7w-3Py9oHeuyZJzPRNFsh2PiEG-ujWwwZrOqKQdk6dftIsszjVfFr1wXfJ3biyALXNyOrdfeFSfeM6sl24CEoSPidSf9AePabqMC6U8D3XAqMoSqTkSSt75CItG2zkhXaEZewjAB8CR21xe17w1yvUEvdQX8vJGmSn65gvXGK64Fl8ivoRiohecsOeemi5yVP%5FroEOze64GcTcazUB%5FHO9A%5F-sORd41RG3PzK7M6UyGe0hqR-mknM8bxyET6o8KH0rvhU-P1lMnB4EeYN10dr6-Wwj4yY9Zzmw%5F1rdB6ziiRINq4W2obir6ZYABcqqBy%5FZNQh5JAXS9EbEdRd7EBvQtduS42ewUK04bH6r8zbU-rUaXe68hldXjIAmH1BfTVpv9E25KNQjqTSMAG0N23xqEe%5FYbuTE1HuCqSq4hTsgJLr8oPU5e4NNfGjoBP3f68ZgvK-OKc%5FFUkOvKTrObAc-Y0tj5DGLVS6GqsIxuqnu4OHeZxjgOwHlZsyyBpg8GGc5cq-qHhK43tx8oOD%5FJ2L9KJAz0l4yrLJ0ZoN3s2wjX7D2iqNY4rQTPKCIui53Qz9Tk2OysCauqoTa5TtmlpK0J14Fb9Cz3FVYYF5jaNdmho0kHqO8A0cWjhRiWiszvfkf-VMCLdhk-BWbQzgQIZkaZXak4rfwkJnaLsivt-Ba%5F2yzUg0534eTq5w6Bq8K33og%5FnfaTdsgs%5F7oRxGw-X2WZC3JHn0gB%5FfPWpiQ&ref=fdaweb.com). “Over the past decade, scientific advancements have led to more approvals of targeted therapies for which efficacy may plateau before reaching the MTD.” For these therapies, a lower dose can provide similar efficacy with improved safety/tolerability for patients, it says.

FOCR’s analysis also notes that dosing PMRs designed to evaluate a lower dose have a median of five years to be completed after approval and evaluations of alternative doses/dosages have a median of 4.2 years. “During this time, there is a risk of patients being exposed to suboptimal doses,” it says, adding that study designs and analytical methods to “support timely identification of the optimal dose other than the MTD approach, is paramount given the length of time it takes to evaluate lower and alternative dose(s).”

Additionally, the FOCR analysis says that the increased focus on dosages dovetails with FDA’s Oncology Center for Excellence’s (OCE) recent efforts to reform approaches to dose optimization. “As more of these targeted therapies are introduced, there will be a need to develop tailored dose optimization strategies that account for the nuances that exist between drugs and drug classes,” FOCR says. “As such, opportunities to adapt dosing strategies and identify appropriate flexibilities that enable timely identification of the optimal dose will be important.

“While PMRs remain an important tool for exercising regulatory flexibility,” the analysis continues, “they may be more appropriate for dosing questions that can be efficiently answered. The dosing evaluations that take longer, such as the exploration of a range of lower doses, could be prioritized earlier in development to avoid exposing patients to potentially suboptimal doses. Leveraging scientific advances and innovative trial designs can help enhance dose optimization strategies and enable more efficient dosing studies in the premarket setting. For instance, the use of novel biomarkers, such as circulating tumor DNA (ctDNA), also holds promise by providing less invasive and real-time insights into tumor dynamics and treatment responses associated with different dosages.”