Biased Evaluation in Cancer Drug Trials—How Use of Progression-Free Survival as the Primary End Point Can Mislead

The goal of any cancer treatment is to improve the duration and/or quality of patient survival. In recent years, only approximately 50% of the anticancer drugs approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have been shown to improve overall survival (OS) and/or a validated measure of quality of life (QoL). Most contemporary randomized clinical trials evaluating anticancer drugs use progression-free survival (PFS) as the primary end point.¹ Both the FDA and EMA accept a significant improvement in PFS for the registration of drugs for most types of cancer, although PFS is rarely a surrogate for OS. Designating PFS instead of OS as the primary end point may provide results more quickly: tumors progress before patients die, so “events” occur earlier, but the reduction in study time is usually modest.² For many new drugs that have been shown to improve PFS, subsequent analysis has demonstrated no improvement in OS or QoL, but these drugs are rarely withdrawn from the market.