Jun Yin1, Mohamed E Salem2, Jesse G Dixon1, Zhaohui Jin3, Romain Cohen4, Aimery DeGramont5, Eric Van Cutsem6, Julien Taieb7, Steven R Alberts3, Norman Wolmark8, Hans-Joachim Schmoll9, Leonard B Saltz10, Thomas J George11, Richard R M Goldberg12, Rachel Kerr13, Sara Lonardi14, Takayuki Yoshino15, Greg Yothers16, Axel Grothey17, Thierry Andre4, Qian Shi1. 1. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. 2. Levine Cancer Institute, Charlotte, NC, USA. 3. Department of Oncology, Mayo Clinic, Rochester, MN, USA. 4. Department of Medical Oncology, Saint-Antoine Hospital, Sorbonne University, Paris, France. 5. Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France. 6. Digestive Oncology, University Hospitals Gasthuisberg Leuven and University of Leuven, Leuven, Belgium. 7. Sorbonne Paris Cité, Paris Descartes University Georges Pompidou European Hospital, Paris, France. 8. Department of Clinical Trials, Alleghany Health Networ k, Pittsburgh, PA, USA. 9. University Clinic Halle (Saale), Halle Martin-Luther-University, Halle, Germany. 10. Memorial Sloan Kettering Cancer Center, New York, NY, USA. 11. University of Florida Health Cancer Center, Gainesville, FL, USA. 12. West Virginia University Cancer Institute, the Mary Babb Randolph Cancer Center, Morgantown, WV, USA. 13. Adjuvant Colorectal Cancer Group, University of Oxford, Oxford, UK. 14. Department of Oncology, Veneto Institute of Oncology IRCCS, Padova PD, Italy. 15. Department of Gastrointestinal Oncology, National Cancer Center, Tokyo, Japan. 16. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA. 17. West Cancer Center, Germantown, TN, USA.
Abstract
BACKGROUND: Disease-free survival (DFS) with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival (OS) with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence in patients who received adjuvant FOLFOX. Hence, reevaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. METHODS: Individual patient data from 9 randomized studies conducted between 1998 and 2009 were included; 3 trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (RWLS2) and Copula bivariate (RCopula2) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. RESULTS: Data from a total of 18 396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (T1-3 and N1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high or deficient mismatch repair tumors. Trial-level correlation between 3-year DFS and 5-year OS remained strong (RWLS2 = 0.82, 95% CI = 0.67 to 0.98; RCopula2 = 0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. CONCLUSIONS: Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.
BACKGROUND: Disease-free survival (DFS) with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival (OS) with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence in patients who received adjuvant FOLFOX. Hence, reevaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. METHODS: Individual patient data from 9 randomized studies conducted between 1998 and 2009 were included; 3 trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (RWLS2) and Copula bivariate (RCopula2) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. RESULTS: Data from a total of 18 396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (T1-3 and N1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high or deficient mismatch repair tumors. Trial-level correlation between 3-year DFS and 5-year OS remained strong (RWLS2 = 0.82, 95% CI = 0.67 to 0.98; RCopula2 = 0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. CONCLUSIONS: Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.
Authors: Marzieh Araghi; Isabelle Soerjomataram; Mark Jenkins; James Brierley; Eva Morris; Freddie Bray; Melina Arnold Journal: Int J Cancer Date: 2019-01-08 Impact factor: 7.396
Authors: Steven R Alberts; Daniel J Sargent; Suresh Nair; Michelle R Mahoney; Margaret Mooney; Stephen N Thibodeau; Thomas C Smyrk; Frank A Sinicrope; Emily Chan; Sharlene Gill; Morton S Kahlenberg; Anthony F Shields; James T Quesenberry; Thomas A Webb; Gist H Farr; Barbara A Pockaj; Axel Grothey; Richard M Goldberg Journal: JAMA Date: 2012-04-04 Impact factor: 56.272
Authors: D Sargent; Q Shi; G Yothers; E Van Cutsem; J Cassidy; L Saltz; N Wolmark; B Bot; A Grothey; M Buyse; A de Gramont Journal: Eur J Cancer Date: 2011-01-21 Impact factor: 9.162
Authors: J Philip Kuebler; H Samuel Wieand; Michael J O'Connell; Roy E Smith; Linda H Colangelo; Greg Yothers; Nicholas J Petrelli; Michael P Findlay; Thomas E Seay; James N Atkins; John L Zapas; J Wendall Goodwin; Louis Fehrenbacher; Ramesh K Ramanathan; Barbara A Conley; Patrick J Flynn; Gamini Soori; Lauren K Colman; Edward A Levine; Keith S Lanier; Norman Wolmark Journal: J Clin Oncol Date: 2007-04-30 Impact factor: 44.544
Authors: Hans-Joachim Schmoll; Josep Tabernero; Jean Maroun; Filippo de Braud; Timothy Price; Eric Van Cutsem; Mark Hill; Silke Hoersch; Karen Rittweger; Daniel G Haller Journal: J Clin Oncol Date: 2015-08-31 Impact factor: 44.544
Authors: Eric Van Cutsem; Roberto Labianca; György Bodoky; Carlo Barone; Enrique Aranda; Bernard Nordlinger; Claire Topham; Josep Tabernero; Thierry André; Alberto F Sobrero; Enrico Mini; Richard Greil; Francesco Di Costanzo; Laurence Collette; Laura Cisar; Xiaoxi Zhang; David Khayat; Carsten Bokemeyer; Arnaud D Roth; David Cunningham Journal: J Clin Oncol Date: 2009-05-18 Impact factor: 44.544
Authors: Leonard B Saltz; Donna Niedzwiecki; Donna Hollis; Richard M Goldberg; Alexander Hantel; James P Thomas; Anthony L A Fields; Robert J Mayer Journal: J Clin Oncol Date: 2007-08-10 Impact factor: 44.544
Authors: M E Salem; J Yin; R M Goldberg; L D Pederson; N Wolmark; S R Alberts; J Taieb; J L Marshall; S Lonardi; T Yoshino; R S Kerr; G Yothers; A Grothey; T Andre; A De Gramont; Q Shi Journal: Ann Oncol Date: 2020-01-16 Impact factor: 32.976