Evaluation of Progression-Free Survival as a Surrogate Endpoint for Survival in Chemotherapy and Targeted Agent Metastatic Colorectal Cancer Trials
A partir d'une revue de la littérature publiée depuis 2000 (69 essais ayant inclus un total de 20 438 patients), cette étude évalue la pertinence d'utiliser le critère de la survie sans progression en substitution du critère de jugement basé sur la survie globale dans le cadre des essais cliniques de traitements du cancer colorectal métastatique
Pooled analyses of chemotherapy trials in metastatic colorectal cancer (mCRC) have suggested that progression-free survival (PFS) is a surrogate endpoint for overall survival (OS). However, this has not been evaluated under current standard of care regimens of chemotherapy in combination with targeted therapies. We conducted an analysis of published mCRC trials of chemotherapy and targeted therapies since 2000 to evaluate the surrogacy of PFS and response rate (RR) for OS. Study-level data was pooled from 24 randomized mCRC trials that evaluated fluoropyrimidine-based regimens and included trials conducted with targeted agents (panitumumab, cetuximab, bevacizumab, and aflibercept). A total of 69 treatment arms with a sample size of 20,438 patients were included. Linear regression analysis was performed to estimate the correlation of PFS and RR with OS. The correlation coefficient between PFS hazard ratios (HRs) and OS HRs was 0.86 for all trials, 0.89 for 12 phase III trials of targeted agents in combination with chemotherapy, 0.95 for 8 first-line phase III trials of targeted agents, and 0.83 for 9 trials of anti-EGFR-targeted agents. In all cases, correlation coefficients between RR and OS HRs were lower than those between PFS HRs and OS HRs (values ranging from 0.42 to 0.81). In this study-level analysis of randomized mCRC trials of chemotherapy and targeted agents, improvements in PFS are strongly correlated with improvements in OS. This suggests that PFS remains a valid surrogate endpoint for OS with current treatment regimens in the mCRC setting.
Clinical Cancer Research , résumé, 2013