Buyse M et al. (2007) Progression-free survival is a surrogate for survival in advanced colorectal cancer. J Clin Oncol 25: 5218–5224

Overall survival (OS) is often used as an end point in trials evaluating the efficacy of treatments in colorectal cancer, but measuring this outcome requires prolonged follow-up and the effects of first-line therapies can be influenced by the effects of subsequent therapies.

Buyse et al. retrospectively analyzed data on OS and progression-free survival (PFS) from 13 trials of chemotherapy in advanced colorectal cancer to assess whether PFS could be used as a surrogate for OS in this setting. Ten of these studies were historical trials comparing fluorouracil plus leucovorin with fluorouracil or raltitrexed, whereas three were validation trials of fluorouracil plus leucovorin with or without irinotecan or oxaliplatin.

First, the authors compared OS and PFS from the historical trials (median follow-up 30.4 months) to determine the correlation between these end points. OS and PFS showed a strong correlation (rank correlation coefficient 0.82). The correlation between the effects of treatment on these end points was also high (correlation coefficient 0.99), but it dropped when a particularly influential trial was excluded (correlation coefficient 0.74). The historical trial statistics were then applied to the PFS data in the validation trials to test whether PFS could predict OS. The resulting estimated OS values agreed well with the observed (actual) OS.

The authors conclude that PFS can be used to reliably predict OS in advanced colorectal cancer trials, and that it can, therefore, be used as an alternative primary efficacy end point to avoid the limitations associated with the use of OS.