PURPOSE: The validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment. METHODS: We conducted a systematic literature review of mCRC phase 2 and 3 clinical trials that reported OS and PFS (or time-to-progression [TTP]) data. Correlation between endpoints (either PFS alone or PFS aggregated with TTP [PFS_TTP]) was estimated within treatment arms. Treatment effect was the ratio of the median time to OS, PFS, or PFS_TTP in the "control" versus "experimental" arm. We conducted meta-regression analyses and performed receiver-operating characteristic (ROC) analysis. RESULTS: We analyzed data from 62 articles (23,527 patients). A high positive correlation was found between median PFS_TTP and median OS within treatment arms (r = 0.87; 95% confidence interval [CI], 0.82-0.91) and also between the median OS and median PFS (r = 0.89, 95% CI, 0.83-0.93)]. R(2) was 0.48 for PFS_TTP and 0.59 for PFS; R (2) for PFS_TTP was higher for first-line (R(2) = 0.54) than second-line studies (R(2) = 0.38). The ROC analysis is presented as a conceptual tool for evaluating the performance of PFS as a surrogate for OS at various thresholds. CONCLUSIONS: The correlation of PFS, alone or aggregated with TTP, with OS in clinical trials of patients with mCRC is robust across lines of therapy and provides a useful means of predicting improvements in OS using PFS data.
PURPOSE: The validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment. METHODS: We conducted a systematic literature review of mCRC phase 2 and 3 clinical trials that reported OS and PFS (or time-to-progression [TTP]) data. Correlation between endpoints (either PFS alone or PFS aggregated with TTP [PFS_TTP]) was estimated within treatment arms. Treatment effect was the ratio of the median time to OS, PFS, or PFS_TTP in the "control" versus "experimental" arm. We conducted meta-regression analyses and performed receiver-operating characteristic (ROC) analysis. RESULTS: We analyzed data from 62 articles (23,527 patients). A high positive correlation was found between median PFS_TTP and median OS within treatment arms (r = 0.87; 95% confidence interval [CI], 0.82-0.91) and also between the median OS and median PFS (r = 0.89, 95% CI, 0.83-0.93)]. R(2) was 0.48 for PFS_TTP and 0.59 for PFS; R (2) for PFS_TTP was higher for first-line (R(2) = 0.54) than second-line studies (R(2) = 0.38). The ROC analysis is presented as a conceptual tool for evaluating the performance of PFS as a surrogate for OS at various thresholds. CONCLUSIONS: The correlation of PFS, alone or aggregated with TTP, with OS in clinical trials of patients with mCRC is robust across lines of therapy and provides a useful means of predicting improvements in OS using PFS data.
Authors: Kent R Johnson; Clare Ringland; Barrie J Stokes; Danielle M Anthony; Nick Freemantle; Alar Irs; Suzanne R Hill; Robyn L Ward Journal: Lancet Oncol Date: 2006-09 Impact factor: 41.316
Authors: 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; Aimery De Gramont Journal: J Clin Oncol Date: 2005-10-31 Impact factor: 44.544
Authors: Wanling Xie; Susan Halabi; Jayne F Tierney; Matthew R Sydes; Laurence Collette; James J Dignam; Marc Buyse; Christopher J Sweeney; Meredith M Regan Journal: JNCI Cancer Spectr Date: 2019-02-06
Authors: Tasos Papanikos; John R Thompson; Keith R Abrams; Nicolas Städler; Oriana Ciani; Rod Taylor; Sylwia Bujkiewicz Journal: Stat Med Date: 2020-01-28 Impact factor: 2.373