FDA/ASCO Unite on Oncology Optimal Dosing
FDA and American Society of Clinical Oncology (ASCO) researchers are urging drug makers to abandon outdated drug dosing strategies that are potentially putting cancer patients at risk. Their just-posted article in the Journal of Clinical Oncology lays out a new scientific framework aimed at ensuring patients receive cancer treatments that are both effective and tolerable — not simply the highest dose they can endure.
The move is part of FDA’s Project Optimus, an initiative launched in 2021 to overhaul how doses are selected for new cancer drugs. The agency finalized new guidance in 2024 requiring drug developers to optimize dosage before a drug is approved, rather than relying on postmarket studies that often fail to materialize.
The authors say that for decades, many cancer drugs have been tested and approved based on the maximum tolerated dose — essentially, the highest amount of drug patients can take before severe side effects occur. This approach evolved during the era of chemotherapy but is now widely used even for modern immunotherapies and targeted treatments, they write.
According to the authors, this “one-size-fits-all” approach can lead to unnecessary toxicities, forcing patients to stop treatment or reduce their dosage. Notably, the article cites survey data showing that more than half of oncologists already lower starting doses in real-world practice to minimize side effects — often without strong evidence about how it affects effectiveness.
“The idea that higher doses are always better is a misconception,” said FDA and ASCO, which co-sponsored recent workshops on the issue. “Many newer cancer drugs do not show additional benefit at higher doses but do increase the risk of harm.”
The article lays out five scientific principles to guide this new shift forward:
- Collect more comprehensive safety data, including milder but persistent side effects that impact patients’ quality of life.
- Tailor dose-finding studies to the specific drug and patient population, recognizing that older adults and people with comorbidities may tolerate drugs differently.
- Use modern trial designs, such as randomized dose-ranging studies, instead of just small, early-phase trials focused on toxicity.
- Expand clinical trial eligibility to include more representative patients, especially those often excluded due to age, health status, or coexisting conditions.
- Refine pharmacology models to understand how drug exposure correlates with both efficacy and toxicity — including the use of patient-reported outcomes and blood-based biomarkers.
FDA officials emphasized that optimizing dosage is not about slowing down drug development. Rather, they said, it’s about building smarter, more efficient development plans that benefit patients from day one. While the article acknowledges that changing entrenched clinical trial practices will be difficult, it argues that the cost of inaction is too high. Cancer patients deserve treatments that are as safe as they are effective, especially when therapies are taken for months or years.
The authors call for those in the cancer research ecosystem to help implement the changes. Institutional review boards and oversight committees are also urged to scrutinize unnecessary trial restrictions that exclude real-world patients. As drug development becomes increasingly global, FDA says it will work with international regulators to align on dosing best practices.