More than two years after the Food and Drug Administration held a public workshop on measuring overall survival (OS) in clinical cancer trials, the agency has released a draft guidance on the topic recommending that OS be used as a primary endpoint whenever feasible.
The draft guidance, published on Aug. 18, will be accepting comments until Oct. 20.
Even when OS is not used as the primary endpoint, the FDA still advises that trial sponsors collect and submit survival data to the regulator.
“In some situations, overall survival may be a secondary endpoint included in a pre-specified hypothesis testing plan,” the FDA wrote in the guidance. Even if not a secondary endpoint, “FDA has historically evaluated the overall survival results in a descriptive manner” as a safety measurement.
The American Society of Clinical Oncology agrees with the FDA’s recommendation, the organization’s chief medical officer and executive vice president Julie Gralow, M.D., told Fierce Biotech.
“ASCO agrees that overall survival remains the gold standard endpoint in oncology and supports the recommendation that all randomized oncology clinical trials should be designed to assess overall survival to appropriately evaluate potential harm,” Gralow said.
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Gralow also agreed with the agency that, in certain situations, OS may not be the best choice for a primary endpoint. This includes when survival times are long, requiring extensive follow-up to determine the experimental treatment has benefit, or in single-arm trials where there is no existing OS data to compare results to.
The FDA also suggests assessing OS during interim analyses to help determine if the tested therapy is futile or unsafe, which ASCO is also aligned with.
“When considering OS as a safety endpoint, differences in OS would be expected to be seen relatively early and we agree that these should be planned for independent data monitoring committee charters,” Gralow said.
If OS data are unclear, but other intermediate endpoints seem to show a clinical benefit, then accelerated approval might be the best regulatory path forward, the FDA wrote.
“Traditional approval can then be considered at a later time when there are sufficiently robust and interpretable overall survival results available,” the guidance says.
The new guidance stems from a Biden-era workshop held in North Bethesda, Maryland in July 2023. Jointly held by the FDA, American Association for Cancer Research and American Statistical Association, the workshop brought together oncology experts to discuss the use of OS in clinical trials and techniques for properly measuring it.
