Overall survival benefits of cancer drugs initially approved by the US Food and Drug Administration on the basis of...

Area of Science:

• Oncology
• Clinical Pharmacology
• Regulatory Science

Background:

• Cancer drugs are often approved by the US Food and Drug Administration (FDA) using surrogate endpoints before overall survival data are mature.
• This practice can lead to uncertainty regarding the true long-term benefit of these novel therapies.

Purpose of the Study:

• To assess if cancer drugs approved with immature survival data demonstrate an overall survival benefit post-marketing authorization.
• To investigate where and when this post-approval survival evidence is reported.

Main Methods:

• A retrospective analysis of FDA-approved cancer drug indications between 2001 and 2018 was conducted.
• Data on post-approval overall survival results were systematically collected from FDA labeling, PubMed, and ClinicalTrials.gov.
• The primary outcome was the availability of statistically significant overall survival benefits after marketing authorization.

Main Results:

• Of 39 indications approved with immature survival data, 97% had subsequent survival data available.
• Only 32% of these indications showed a statistically significant overall survival benefit, while 63% yielded non-significant findings with mature data.
• Evidence of statistically significant overall survival benefit was reported a median of 1.5 years post-approval, but non-significant results took longer to emerge.

Conclusions:

• Fewer than one-third of cancer drug indications initially approved with immature survival data ultimately demonstrated a statistically significant overall survival benefit.
• Significant inconsistencies in the timing and availability of post-approval survival data across reporting sources necessitate enhanced reporting standards.