Document Detail

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
Related Documents :
23302469 - Interactions of mir-323/mir-326/mir-329 and mir-130a/mir-155/mir-210 as prognostic indi...
24334919 - Associations of pretreatment serum total testosterone measurements with pathology-detec...
24331189 - Therapy-related myelodysplasia and acute myeloid leukemia.
24761809 - 'double-hit' cytogenetic status may not be predicted by baseline clinicopathological ch...
24128789 - High expression of glycolytic and pigment proteins is associated with worse clinical ou...
24858459 - Clinico-pathological predictive factors in squamous cell carcinoma of the tongue and th...
24401669 - Intensity-modulated radiation therapy for anal cancer: results from a multi-institution...
24845799 - Ipss-r in 555 taiwanese patients with primary mds: integration of monosomal karyotype c...
9793029 - Effective treatment of thymic carcinoma with operation and combination chemotherapy aga...
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Interleukin 15 provides relief to CTLs from regulatory T cell-mediated inhibition: implications for ...
Next Document:  Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy ...