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Progression-Free Survival as a Surrogate Endpoint for Median Overall Survival in mCRC: Literature-Based Analysis from 50 Randomized First-Line Trials.
MedLine Citation:
PMID:  23149819     Owner:  NLM     Status:  Publisher    
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.
Clemens Giessen; Rudiger P Laubender; Donna P Ankerst; Sebastian Stintzing; Dominik P Modest; Ulrich Mansmann; Volker Heinemann
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-13
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  -     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, Ludwig-Maximilians-University of Munich, Germany.
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