Meta-regression of treatments for metastatic colorectal cancer: Quantifying incremental benefit from 2000 to 2012

To evaluate the overall effectiveness of treatments for metastatic colorectal cancer, a meta-regression was undertaken in which randomized studies from 2000 to 2012 were evaluated and the temporal trend for both overall survival (OS) and progression-free survival (PFS) was determined. Our literature search was essentially based on PubMed but information sources were scanned. Trials were included if a fluoropyrimidine regimen was given to at least one arm and information on PFS and OS was available. Medians for OS and PFS were our end-points. Covariates included temporal trend, arm allocation and Kirsten rat sarcoma status. In analyzing 130 treatment arms identified through our literature search, meta-regression showed an improvement with time for both OS (P < 0.001) and PFS (P < 0.001). The increase in median OS was from 14.9 mo in 2000 to 18.8 mo in 2012. Likewise, the improvement in PFS was from 5.7 to 8.1 mo. Multivariate analysis confirmed these findings. A post-hoc multivariate analysis was focused on patient arms treated with bevacizumab (n = 17) or without bevacizumab (n = 113); the multivariate-adjusted improvement attributable to bevacizumab was 1.66 mo for OS (P = 0.071) and 1.59 mo for PFS (P = 0.002). Overall, our results indicate that OS and PFS have improved from 2000 to 2012 but the extent of this improvement is small and seems to have quite a questionable clinical relevance.