Progression-free survival in oncology: Caveat emptor!

Overall survival (OS) is the undisputed gold standard efficacy end-point in cancer drug trials. It is with growing concern that we observe how progression-free survival (PFS) gains ground as surrogate end-point in its place. PFS has appeal because it is resource-efficient, but it has severe shortcomings. Our concern is that uncritical use of PFS will harm the evidence-based evaluation of cancer drugs when considering them for standard use in publicly financed health care systems. PFS is only valid as a surrogate end-point for OS if it correlates strongly with OS and if the cancer drug being investigated has the same effect on PFS and OS such that effects on one predict effects on the other. The latter might be less obvious than the former but is no less critical. Research indicates that in a majority of cases, correlation between surrogate end-points and OS is of medium strength or lower. PFS is therefore unreliable as a surrogate for OS. We do not find it justified to use PFS as surrogate for OS without first having assessed its validity. Stakeholders who take part in evaluating cancer drugs considered for standard use in a health care system must be particularly vigilant about this issue to minimize the risk of introducing cancer drugs that have an unacceptable cost-risk-benefit profile.