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Recommendations for the assessment of progression in randomised cancer treatment trials

Published:December 22, 2008DOI:https://doi.org/10.1016/j.ejca.2008.10.042

      Abstract

      Progression-free survival (PFS) is an increasingly important end-point in cancer drug development. However, several concerns exist regarding the use of PFS as a basis to compare treatments. Unlike survival, the exact time of progression is unknown, so progression times might be over-estimated (or under-estimated) and, consequently, bias may be introduced when comparing treatments. In addition, the assessment of progression is subject to measurement variability which may introduce error or bias. Ideally trials with PFS as the primary end-point should be randomised and, when feasible, double-blinded. All patients eligible for study should be evaluable for the primary end-point and thus, in general, have measurable disease at baseline. Appropriate definitions should be provided in the protocol and data collected on the case-report forms, if patients with only non-measurable disease are eligible and/or clinical, or symptomatic progression are to be considered progression events for analysis. Protocol defined assessments of disease burden should be obtained at intervals that are symmetrical between arms. Independent review of imaging may be of value in randomised phase II trials and phase III trials as an auditing tool to detect possible bias.

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      References

        • Buyse M.
        • Burzykowski T.
        • Carroll K.
        • et al.
        Progression-free survival is a surrogate for survival in advanced colorectal cancer.
        J Clin Oncol. 2007; 25: 5218-5224
        • Burzykowski T.
        • Buyse M.
        • Piccart-Gebhart M.J.
        • et al.
        Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.
        J Clin Oncol. 2008; 26: 1987-1992
      1. US Department of Health and Human Services FaDA. Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. <http://www.fda.gov/cder/guidance/7478fnl.pdf>; 2007 [accessed 19.08.08].

      2. (CHMP) CfMPfHU. Guideline on the evaluation of anticancer medicinal products in man. European Medicines Agency 7 Westferry Circus, Canary Wharf, London E14 4HB, UK; 2005.

        • Bogaerts J.
        • Ford R.
        • Sargent D.
        • et al.
        Individual patient data analysis to assess modifications to the RECIST criteria.
        Eur J Cancer. 2009; 45: 248-260
      3. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: Revised RECIST guideline (version1.1). Eur J Cancer, 2009;45:228–47.

        • Panageas K.S.
        • Ben-Porat L.
        • Dickler M.N.
        • Chapman P.B.
        • Schrag D.
        When you look matters: the effect of assessment schedule on progression-free survival.
        J Natl Cancer Inst. 2007; 99: 428-432
        • Carroll K.J.
        Analysis of progression-free survival in oncology trials: some common statistical issues.
        Pharm Stat. 2007; 6: 99-113
      4. Kane R, Yang P. FDA presentation: genasense (Oblimersen) for metastatic melanoma <http://www.fda.gov/ohrms/dockets/ac/04/slides/4037s1.htm>; 2004 [accessed 19.08.08].

        • Ruan P.K.
        • Gray R.J.
        Sensitivity analysis of progression-free survival with dependent withdrawal.
        Stat Med. 2008; 27: 1180-1198
        • Dodd L.E.
        • Korn E.L.
        • Freidlin B.
        • et al.
        Blinded independent central review of progression-free survival in phase III clinical trials: important design element or unnecessary expense?.
        J Clin Oncol. 2008; 26: 3791-3796
        • Stone A.
        • Wheeler C.
        • Carroll K.
        • Barge A.
        Optimizing randomized phase II trials assessing tumor progression.
        Contemp Clin Trials. 2007; 28: 146-152
        • Stone A.
        • Wheeler C.
        • Barge A.
        Improving the design of phase II trials of cytostatic anticancer agents.
        Contemp Clin Trials. 2007; 28: 138-145