USA – FDA Should Reassess Postmarket Trials for Cancer Drugs Approved via Accelerated Pathway, Researchers Say

The US Food and Drug Administration (FDA) may need to reassess how confirmatory trials are conducted after just one-fifth of such trials for cancer drug indications approved via FDA’s accelerated approval pathway have demonstrated improvements in overall survival (OS), researchers reported Tuesday in JAMA Internal Medicine research.

The researchers looked at 93 cancer drug indications granted accelerated approval by FDA from 1992 through May 2017, finding confirmatory trials reported that 20% had improvement in overall survival, 21% had improvement in a different surrogate measure and 20% had improvement in the same surrogate measure used in confirmatory trials and preapproval trials.

“Appropriate use of surrogates for accelerated approval requires an appreciation for how the validity of a surrogate can vary from one indication to another. One strategy for capturing this variability would be to have a continually updated database of strengths of surrogate validation across tumor types as results from newer trials become available,” the researchers from the Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School said.

They also called to adapt FDA’s recently published list of surrogate measures to include the strengths of surrogacy validation. “Confirming the clinical benefit of a cancer drug using the same surrogate measure as the one used in its preapproval trial should be reserved for when the surrogate measure for a given indication has been validated,” they added.