Progression-Free Survival Should Not Be Used as a Primary End Point for Registration of Anticancer Drugs
Ce dossier présente deux articles concernant l'évaluation des anticancéreux dans le cadre d'une demande d'autorisation de mise sur le marché : l'un examinant la pertinence de la survie sans progression comme premier critère de jugement, l'autre analysant la pertinence d'utiliser des critères de jugement de substitution à la survie globale
In 2012, two of us wrote in these pages a critique arguing against the use of progression-free survival (PFS) as a primary end point in randomized controlled trials (RCTs) evaluating anticancer drugs.1 Drugs should be approved if there is evidence that they benefit patients in comparison with best standard care. Regardless of medical disease, one can only benefit patients by improving their duration or quality of survival. Despite evidence summarized below that PFS is rarely a surrogate for overall survival (OS) or quality of life (QoL), PFS is accepted by the US Food and Drug Administration (FDA) and the European Medicines Agency as an end point for registration and marketing of anticancer drugs. Consequently, PFS is now the most common primary end point in oncology RCTs. In a review of RCTs published during 2010-2020, 42% of breast, colorectal, and non–small-cell lung cancer (NSCLC) trials used PFS and only 29% used OS as a primary end point.2 This is a striking change: during 1995-2004 and 2005-2009, PFS and OS were the primary end point in 0%/49% and 18%/36%, respectively.3,4 Recently, we have learnt more about the failure of apparent improvements in PFS to predict improvements in OS, about biases that confound its interpretation, and about patients' misunderstanding of PFS such that many believe that longer PFS indicates improved survival. A decade after our original critique, there are more reasons for concern about the use of PFS as a primary end point in oncology trials designed to inform practice (...)