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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/7071

Title: Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20,898 patients on 18 tandomized trials
Authors: Sargent, Daniel J.
Wieand, Harry S.
Haller, Daniel G.
Gray, Richard
Benedetti, Jacqueline
Buyse, Marc
Labianca, Roberto
Seitz, Jean Francois
O'Callaghan, Christopher J.
Francini, Guido
Grothey, Axel
O'Connell, Michael
Catalano, Paul J.
Blanke, Charles D.
Kerr, David
Green, Erin
Wolmark, Norman
André, Thierry
Goldberg, Richard M.
De Gramont, Aimery
Issue Date: 2005
Citation: Journal of clinical oncology, 23(34). p. 8664-8670
Abstract: Purpose A traditional end point for colon adjuvant clinical trials is overall survival (OS), with 5 years demonstrating adequate follow-up. A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice. Methods Individual patient data were pooled from 18 randomized phase III colon cancer adjuvant clinical trials. Trials included 43 arms, with a pooled sample size of 20,898 patients. The primary hypothesis was that disease-free survival (DFS), with 3 years of follow-up, is an appropriate primary end point to replace CS with 5 years of follow-up. Results The recurrence rates for years 1 through 5 were 12%, 14%, 8%, 5%, and 3%, respectively. Median time from recurrence to death was 12 months. Eighty percent of recurrences were in the first 3 years; 91% of patients with recurrence by 3 years died before 5 years. Correlation between 3-year DFS and 5-year OS was 0.89. Comparing control versus experimental arms within each trial, the correlation between hazard ratios for DFS and CS was 0.92. Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 (92%) of 25 cases. Formal measures of surrogacy were satisfied. Conclusion In patients treated on phase III adjuvant colon clinical trials, DFS and CIS are highly correlated, both within patients and across trials. These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens, although marginally significant DFS improvements may not translate into significant OS benefits.
URI: http://hdl.handle.net/1942/7071
DOI: 10.1200/JCO.2005.01.6071
ISI #: 000233690200018
ISSN: 0732-183X
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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