Progression-free survival as a surrogate endpoint for median overall survival in metastatic colorectal cancer: Literature-based analysis from 50 randomized first-line trials

Clemens Giessen, Ruediger Paul Laubender, Donna Pauler Ankerst, Sebastian Stintzing, Dominik Paul Modest, Ulrich Mansmann, Volker Heinemann

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Purpose: To evaluate progression-free survival (PFS) as a potential surrogate endpoint (SEP) for overall survival (OS) in metastatic colorectal cancer (mCRC) with a focus on applicability to trials containing targeted therapy with anti-VEGF- or anti-EGF receptor (EGFR)-directed monoclonal antibodies. Experimental Design: A systematic literature search of randomized trials of first-line chemotherapy for mCRC reported from January 2000 to January 2012 was conducted. 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 was high across all studies (RTE = 0.87, REP = 0.86). This was also observed in chemotherapy-only trials (RTE = 0.93, R EP = 0.81) but less so for trials containing monoclonal antibodies (RTE = 0.47; REP = 0.52). Limiting the analysis to bevacizumab-based studies (11 trials, 3,310 patients) again yielded high correlations between treatment effects on PFS and on OS (RTE = 0.84), whereas correlation within PFS and OS was low (REP = 0.45). In 7 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 showed 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.

Original languageEnglish (US)
Pages (from-to)225-235
Number of pages11
JournalClinical Cancer Research
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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