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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/7824

Title: Progression-free survival is a surrogate for survival in advanced colorectal cancer
Authors: BUYSE, Marc
Carroll, Kevin
Michiels, Stefan
Sargent, Daniel J.
Miller, Langdon L.
Elfring, Gary L.
Pignon, Jean-Pierre
Piedbois, Pascal
Issue Date: 2007
Citation: JOURNAL OF CLINICAL ONCOLOGY, 25(33). p. 5218-5224
Abstract: Purpose The traditional end point for assessing efficacy of first-line chemotherapies for advanced cancer is overall survival (OS), but this end point requires prolonged follow-up and is potentially confounded by the effects of second-line therapies. We investigated whether progression-free survival (PFS) could be considered a valid surrogate for OS in advanced colorectal cancer. Patients and Methods Individual patient data were available from 10 historical trials comparing fluouracil (FU) + leucovorin with either FU alone (1,744 patients) or with raltitrexed (1,345 patients) and from three validation trials comparing FU + leucovorin with or without irinotecan or oxaliplatin (1,263 patients). Correlation coefficients were estimated in historical trials between the end points of PFS and OS, and between the treatment effects on these end points. Treatment effects on OS were predicted in validation trials, and compared with the observed effects. Results In historical trials, 1,760 patients (57%) had progressed or died at 6 months, and 1,622 (52%) had died at 12 months. The rank correlation coefficient between PFS and OS was equal to 0.82 (95% Cl, 0.82 to 0.83). The correlation coefficient between treatment effects on PFS and on OS ranged from 0.99 (95% Cl, 0.94 to 1.04) when all trials were considered to 0.74 (95% Cl, 0.44 to 1.04) after exclusion of one highly influential trial. In the validation trials, the observed OS hazard ratios were within the 95% prediction intervals. A hazard ratio of 0.77 or lower in terms of PFS would predict a benefit in terms of OS. Conclusion PFS is an acceptable surrogate for OS in advanced colorectal cancer.
Notes: Int Inst Drug Dev, B-1340 Louvain, Belgium. Hasselt Univ, Ctr Stat, Diepenbeek, Belgium. AstraZeneca Res & Dev, Oncol Therapy Area, Macclesfield, Cheshire, England. Inst Gustave Roussy, Biostat & Epidemiol Unit, Villejuif, France. AstraZeneca, Oncol Therapy Area, Rueil Malmaison, France. Mayo Clin, Div Biostat, Rochester, MN USA. PTC Therapeut, S Planfield, NJ USA.Buyse, M, Int Inst Drug Dev, 30 Ave Prov, B-1340 Louvain, Belgium.marc.buyse@iddi.com
URI: http://hdl.handle.net/1942/7824
DOI: 10.1200/JCO.2007.11.8836
ISI #: 000251074400014
ISSN: 0732-183X
Category: A1
Type: Journal Contribution
Validation: ecoom, 2008
Appears in Collections: Research publications

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