Progression-Free Survival Remains Debatable Endpoint in Cancer Trials

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I n recent years the U.S. Food and Drug Administration has approved cancer therapies on the basis of improved progression-free survival (PFS), including several drugs for the treatment of metastatic kidney cancer. Clinicians who treat kidney cancer patients are convinced that the agency made the right move, and some even contend that overall survival (OS) is no longer a useful endpoint in this disease setting. However, despite some support for the use of PFS in one disease setting, its value as a standard endpoint for clinical trials remains a point of debate in oncology as a whole. Some experts argue that OS is the only time-toevent endpoint that shows true benefi t to patients, whereas others think that PFS should be accepted as long as the trials are carried out according to rigorous standards. To hash out some of those issues, academic and industry statisticians gathered Oct. 7 – 9 for the ProgressionFree Survival Oncology Workshop in Bethesda, cosponsored by the Drug Information Association, the FDA, the National Cancer Institute, and the Pharmaceutical Research and Manufacturers of America (PhRMA). Richard Pazdur, M.D. , director of the FDA Offi ce of Oncology Drug Products and the keynote speaker at the meeting, acknowledges that PFS requires a more nuanced risk – benefi t analysis than OS does, but he says that sometimes PFS is an appropriate endpoint for registration trials. “A lot of it has to do with magnitude, magnitude, magnitude,” he said in an interview. “Just demonstrating a statistically signifi cant difference in PFS is not enough. It has to be clinically meaningful.” And he made it clear that even as the agency considers more approvals that are based on PFS, it won’t abandon OS altogether. “We are always still interested in looking at OS and will look at it because OS is not just an effi cacy endpoint but also a safety endpoint.”