Purpose: To evaluate progression-free survival (PFS) as potential surrogate endpoint (SEP) for overall survival (OS) in metastatic colorectal cancer (mCRC) with focus on applicability to trials containing targeted therapy with anti-VEGF- or anti-EGFR directed monoclonal antibodies. Methods: A systematic literature search of randomized trials of first-line chemotherapy for mCRC reported from January 2000 to January 2012 was performed. Adjusted weighted linear regression was used to calculate correlations within PFS and OS (endpoints; REP) and between treatment effects on PFS and on OS (treatment effects; RTE). Results: Fifty trials reflecting 22,736 patients met the inclusion criteria. Correlation between treatment effects on PFS and OS and between the endpoints PFS and OS were high across all studies (RTE = 0.87, REP = 0.86). This was also observed in chemotherapy-only trials (RTE = 0.93, REP = 0.81), but less so for trials containing monoclonal antibodies (RTE = 0.47; REP = 0.52). Limiting the analysis to bevacizumab-based studies (eleven trials, 3,310 patients) yielded again high correlations between treatment effects on PFS and on OS (RTE = 0.84), while correlation within PFS and OS was low (REP = 0.45). In seven trials (1,335 patients) investigating cetuximab or panitumumab-based studies, contrasting correlations with very wide confidence intervals were observed (RTE = 0.28; REP = 0.96). Conclusions: PFS demonstrated consistently high correlation with OS of an order that would justify its use as an SEP in chemotherapy regimens. For validation of surrogacy in anti-VEGF and anti-EGFR-directed therapies, further research and a larger set of trials is needed.
- Received May 9, 2012.
- Revision received October 22, 2012.
- Accepted October 29, 2012.
- Copyright © 2012, American Association for Cancer Research.