[Disease-Free Survival Versus Overall Survival As a Primary End Point for Adjuvant Colon Cancer Studies]
>>JCO Early Release, published online ahead of print Oct 31 2005
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 Randomized Trials
Daniel J. Sargent *, Harry S. Wieand , Daniel G. Haller , Richard Gray , Jacqueline K. Benedetti , Marc Buyse , Roberto Labianca , Jean Francois Seitz , Christopher J. O'Callaghan , Guido Francini , Axel Grothey , Michael O'Connell , Paul J. Catalano , Charles D. Blanke , David Kerr , Erin Green , Norman Wolmark , Thierry Andre , Richard M. Goldberg , and Aimery De Gramont
From the North Central Cancer Treatment Group, Mayo Clinic, Rochester, MN; National Surgical Adjuvant Breast and Bowel Project Statistical Center and Operations Office, Pittsburgh; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; QUASAR Collaborative Group, Birmingham and Oxford, United Kingdom; Southwest Oncology Group Statistical Center, Seattle, WA; International Drug Development Institute, Brussels, Belgium; Ospedali Riuniti, Bergamo; University of Siena, Siena, Italy; University of the Mediterranean, Marseilles; Groupe d'Etude et de Recherche Clinique en Oncologie et Radiothérapie, Paris; Hospital Saint Antoine, Paris, France; National Cancer Institute of Canada Clinical Trials Group, Queens University, Kingston, Ontario, Canada; Eastern Cooperative Oncology Group Statistical Center, Boston, MA; Oregon Health and Science University Cancer Institute, Portland, OR; and University of North Carolina, Chapel Hill, NC.
* To whom correspondence should be addressed. E-mail: sargent.daniel@mayo.edu
Background: 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 OS 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 OS 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 OS 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.<<
Kind of on topic.
Cheers, Tuck |
