Researchers concerned by underutilization of accelerated approval in oncology
Most adult cancer drugs approved by the US Food and Drug Administration (FDA) over the past two decades were regular approvals for expanded indications based on surrogate endpoints, rather than accelerated approvals, according to a study published in JAMA on Thursday.
The study, authored by, also observed that the number of approvals based on single-arm trials and based on response rate is on the rise.
To conduct the study, authors Brian Shkabari and colleagues at the Sinclair Cancer Research Institute in Kingston, Ontario, Canada, conducted a cross-sectional analysis of 385 adult cancer drug approvals between 1 January 2006 and 31 December 2025 to examine changes in the use of regulatory pathways, drug types, trial designs, and quality of evidence. The objective, they wrote, was to assess whether and how the landscape for cancer drug approvals may have changed, given updated guidance on the accelerated approval pathway, confirmatory trial requirements, and survival assessments.
The authors raised concerns about several trends, including a decline in approvals based on overall survival and progression-free survival in favor of response rate, as well as an increase in regular approvals based on weaker evidence. “This underutilization of accelerated approval by offering up-front regular approval based on surrogate measures is problematic because it removes the safety net of confirmatory trials to verify clinical benefit and safety required by accelerated approval,” the authors wrote.
Approvals of nononcologic, diagnostic, hematological, pediatric, and biosimilar or generic drugs, as well as dosage changes and reformulations were excluded from the study.
The researchers also took a more granular look at the data, examining approvals between 2006 and 2010, 2011 and 2015, 2016 and 2020, and 2021 and 2025 to see if there were any significant trends. Overall, what they found was that between 2006 and 2025 FDA approved 154 (40%) novel adult cancer drugs and 231 (60%) supplemental new indications of already approved drugs. Of those total approvals, over a quarter of the drugs were approved under an accelerated approval pathway, and the remainder were indication approvals for advanced cancer.
"The majority of the FDA approvals for cancer medicines in 2006-2025 were indication expansion for existing drugs, regular approvals, and based on surrogate end points," said the researchers.
The proportion of chemotherapy approvals during that time diminished significantly. "While chemotherapy constituted 40.0% of all approvals in 2006- 2010, it constituted 3.9% of approvals in 2021-2025," they added. "Chemotherapy approvals were almost always regular approvals (28/29 [97%])."
Targeted therapies and immunotherapies accounted for the lion's share of cancer drug approvals between 2006 and 2025 at 35.1% and 32.7%, respectively.
The research also found that lung cancer drugs accounted for the largest share of overall approvals, at 23.4%, followed by genitourinary cancer drugs at 16.6%, gastrointestinal cancer drugs at 15.3%, and breast cancer drugs at 11.9%. They also noted that the proportion of cancer drugs approved based on a single-arm study has significantly increased. Between 2006 and 2010, approvals based on single-arm studies accounted for 12.9% of cancer drug approvals, but by 2021 and 2025, they accounted for 37.2% of approvals.
"Progression-free survival has previously been documented as the most common end point in cancer drug trials, which has been criticized for lack of surrogacy with clinical outcomes and potential for patient misunderstanding," said the researchers. "However, we found that the majority of recent FDA approvals were not even based on progression-free survival.
"In the last decade, response rate, rather than progression-free survival, has become the most common surrogate end point leading to approval, whose correlation with survival is weaker," they added.
Drugs approved in trials with a primary efficacy endpoint of progression-free survival accounted for 36.7% of drugs between 2006 and 2010, rose to 43.8% between 2011 and 2015, but then fell to 32.9% between 2021 and 2025. Those that used objective response rate, however, grew from 10% between 2006 and 2010 to 42.6% between 2021 and 2025. It is also worth noting that trials with a primary endpoint of overall survival dropped significantly form 40% between 2006 and 2010 to 18.7% between 2021 and 2025.
The researchers noted that past studies have shown that most accelerated approvals were based on response rate endpoints from single-arm trials, but their research shows that the majority of surrogate-based endpoint approvals in recent years were from regular approvals rather than accelerated approvals.
"Continued decline in the proportion of approvals based on overall survival, increase in response rate–based approvals, and underutilization of the accelerated approval pathway all reveal concerning trends," they added.
The researchers also found that while 83.9% of cancer drugs were approved based on phase 3 trials between 2006 and 2010, between 2021 and 2025, that had decreased to 64.8%. Overall, such approvals accounted for 66.7% of cancer drug approvals. On the contrary, only 16.1% of approvals between 2006 and 2010 were based on phase 2 trials, but between 2021 and 2025, that increased to 31%, and overall accounts for 29.1% of drugs approved between 2006 and 2025.
