A new study presented at the American Association of Cancer Research and published in the Journal of the American Medical Association has revealed some discrepancies in the US Food and Drug Administration’s (FDA) accelerated approval pathway for cancer drugs.
The study looked at 46 different cancer drugs that were given accelerated approvals between 2013 and 2017.
The FDA’s accelerated approval process allows approvals of new investigational drugs treating unmet medical needs to be approved by the US regulator before they have gone through all of the required levels of testing in humans.
Using publicly available FDA data, the study identified cancer drugs that received accelerated approval within the five-year time period to determine whether they demonstrated clinical benefit and to evaluate the basis for their conversion to regular approval.
The authors identified that around 63% of accelerated approvals were converted to full approval despite only 43% of investigational cancer drugs showing clinical benefit on overall survival (OS) or an increase in quality-of-life in confirmatory trials completed within the next five years, with a further 15% having no results available within that time period.
Additionally, from 2021 to 2023, the team found that 37% of approvals that had been converted were based on response rate after exploring the evidence used to support the approvals.
Authors have said that the strength of response rates based on tumour shrinkage, with some cases of duration of response data, “cannot by itself determine whether a drug offers patients a clinical benefit,” despite the FDA providing full approval to 14% of drugs that were based on this key trend.
Furthermore, the team has also raised concern in relation to confirmatory trials that extend the use of a drug into new areas, including earlier lines of therapy, potentially not resolving uncertainty about the originally approved indication, despite the FDA needing sufficient clinical confirmation that they work.
“The evidence used to justify these [regulatory] decisions is important,” said Edward Cliff, haematology fellow and postdoctoral fellow, Programme on Regulation, Therapeutics and Law.
“We believe that conversion decisions should be both timely… [and] supported by high-quality clinical outcomes,… [which] is critical to the proper functioning of the accelerated approval pathway,” said Ian Liu from Brigham and Women’s Hospital and Harvard Medical School.