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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/24186

Title: Progression-Free Survival as a Surrogate for Overall Survival in Clinical Trials of Targeted Therapy in Advanced Solid Tumors
Authors: Michiels, Stefan
Saad, Everardo D.
Buyse, Marc
Issue Date: 2017
Publisher: ADIS INT LTD
Citation: DRUGS, 77(7), p. 713-719
Abstract: Over the past 15 years, targeted therapy has revolutionized the systemic treatment of cancer. In parallel, there has been a growing debate on the choice of end points in clinical trials in oncology. This debate basically hinges on the choice between overall survival (OS) and progression-free survival (PFS). PFS is advantageous because it is measured earlier than OS, requires a smaller sample size than OS to achieve the desired power, and is not influenced by cross-over. On the other hand, PFS is prone to measurement error and bias, and may not capture the entire treatment effect on the outcomes of most interest to patients with an incurable disease: a prolonged survival and improved quality of life. Therefore, how can we choose between two imperfect end points? The answer to this question would certainly be made easier if PFS could be demonstrated to be a valid surrogate for OS. The validation of a surrogate end point is best made using individual-patient data (IPD) from randomized trials, which allows for standardized assessments of the patient-level and the trial-level correlations between surrogate and final end points. Proper IPD meta-analytical evaluations for targeted agents have still been rare, and to our knowledge only three studies on this topic are currently available in the metastatic setting: one in breast cancer, one in colorectal cancer and one in lung cancer. Although these three studies suffer from limitations inherent to the availability of IPD and the design of the original clinical trials, they have not been able to validate PFS as surrogate for OS, because only modest correlations were found between these two end points, both at the patient and at the trial level. Even if properly conducted surrogate-endpoint evaluations have thus far been unsuccessful, these evaluations are a step in the right direction and can be expected to be applied on a much larger scale in the era of data sharing of clinical trials.
Notes: [Michiels, Stefan] Gustave Roussy, RDC B2M, Serv Biostat & Epidemiol, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. [Michiels, Stefan] Univ Paris Sud, Univ Paris Saclay, UVSQ, CESP,INSERM,U1018, F-94805 Villejuif, France. [Michiels, Stefan] Gustave Roussy, Ligue Natl Canc Meta Anal Platform, F-94805 Villejuif, France. [Saad, Everardo D.] IDDI, Louvain, Belgium. [Buyse, Marc] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat I BioSt, Hasselt, Belgium. [Buyse, Marc] IDDI, San Francisco, CA USA.
URI: http://hdl.handle.net/1942/24186
DOI: 10.1007/s40265-017-0728-y
ISI #: 000399895600001
ISSN: 0012-6667
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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