In a study reported in The Lancet Oncology, Naci et al identified the degree to which initial U.S. Food and Drug Administration (FDA) approvals of cancer drugs based on immature overall survival data were subsequently followed by reporting of overall survival results.
Study Details
The study involved a search of the Drugs@FDA database to identify cancer drug indications approved between January 2001 and December 2018 on the basis of studies with immature survival data. Data on postapproval overall survival results were collected from labeling (Drugs@FDA), journal publications (MEDLINE via PubMed), and clinical trial registries (ClinicalTrials.gov). The primary outcome measure was availability of statistically significant overall survival benefits during the period after marketing authorization through March 2023.
Key Findings
During the study period, the FDA granted marketing authorization to 223 cancer drug indications, including 95 based on studies with overall survival as an endpoint; of these 95, 39 (41%) had immature survival data.
After a minimum follow-up of 4.3 years after marketing authorization and a median follow-up of 8.2 years (interquartile range [IQR] = 5.3–12.0 years) after FDA approval, additional overall survival data from the pivotal trials became available in revised labeling, publications, or both for 38 (97%) of the 39 indications with immature data.
The subsequently available data showed statistically significant overall survival benefits in 12 (32%) of 38 indications and statistically nonsignificant outcomes for 24 indications (63%).
Statistically significant overall survival benefits were reported in labeling or publications at a median of 1.5 years (IQR = 0.8–2.3 years) after initial approval. The median time to reporting of statistically nonsignificant results was 3.3 years (IQR = 2.2–4.5 years).
The investigators concluded, “Fewer than a third of [cancer drug] indications approved with immature survival data showed a statistically significant overall survival benefit after approval. Notable inconsistencies in timing and availability of information after approval across different sources emphasize the need for better reporting standards.”
Huseyin Naci, PhD, of the Department of Health Policy, London School of Economics and Political Science, is the corresponding author for The Lancet Oncology article.
Disclosure: The investigators reported that there was no external funding for the study. For full disclosures of the study authors, visit thelancet.com.
