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Influence of censoring on conclusions of trials for women with metastatic breast cancer

Published:February 26, 2015DOI:https://doi.org/10.1016/j.ejca.2014.12.016

      Abstract

      Progression-free survival and time-to-progression (PFS/TTP) are used commonly as primary end-points in trials evaluating treatments for metastatic breast cancer (MBC). We reviewed the impact of censoring on interpretation of these end-points. A systematic review identified phase 3 trials in MBC published between 2001 and 2012 that reported hazard ratios (HRs) for PFS/TTP and Kaplan–Meier curves indicating numbers at risk. We calculated HRs for time-to-treatment-failure (TTF) where discontinuation of treatment for any reason is considered an event. Mean HRs for PFS/TTP, TTF, and overall survival (OS) were 0.79, 0.89 and 0.91, respectively. Unbalanced censoring of patients prior to progression was prevalent, usually with more patients censored in the experimental arms. There was moderate-to-poor correlation of HRs of PFS/TTP and TTF with HRs for OS. We suggest that TTF should be reported as supportive analysis in registration trials and extent of missing data due to censoring be considered in decisions made by regulatory agencies.

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      References

        • Korn R.L.
        • Crowley J.J.
        Overview: progression-free survival as an endpoint in clinical trials with solid tumors.
        Clin Cancer Res. 2013; 19: 2607-2612
        • Broglio K.R.
        • Berry D.A.
        Detecting an overall survival benefit that is derived from progression-free survival.
        J Natl Cancer Inst. 2009; 101: 1642-1649
        • Booth C.M.
        • Eisenhauer E.A.
        Progression-free survival: meaningful or simply measurable?.
        J Clin Oncol. 2012; 30: 1030-1033
        • Prentice R.L.
        Surrogate endpoints in clinical trials: definition and operational criteria.
        Stat Med. 1989; 8: 431-440
        • Villaruz L.C.
        • Socinski M.A.
        The clinical viewpoint: definitions, limitations of RECIST, practical considerations of measurement.
        Clin Cancer Res. 2013; 19: 2629-2636
        • Parmar M.K.
        • Torri V.
        • Stewart L.
        Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.
        Stat Med. 1998; 17: 2815-2834
        • Baselga J.
        • Campone M.
        • Piccart M.
        • Burris 3rd, H.A.
        • Rugo H.S.
        • Sahmoud T.
        • et al.
        Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.
        N Engl J Med. 2012; 366: 520-529
        • Piccart M.
        • Hortobagy G.N.
        • Campone M.
        • Pritchard K.I.
        • Lebrun F.
        • Ito Y.
        • et al.
        Everolimus plus exemestane for hormonereceptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2.
        Ann Oncol. 2014; 25: 2357-2362
        • Yan X.
        • Lee S.
        • Li N.
        Missing data handling methods in medical device clinical trials.
        J Biopharm Stat. 2009; 19: 1085-1098
        • Bhattacharya S.
        • Fyfe G.
        • Gray R.J.
        • Sargent D.J.
        Role of sensitivity analyses in assessing progression-free survival in late-stage oncology trials.
        J Clin Oncol. 2009; 27: 5958-5964
      1. FDA May 2007. Guidance for Industry: Clinical Trail Endpoints the Approval of Cancer Drugs and Biologics. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071590.pdf [accessed October 07, 2014].