Exploring and validating surrogate endpoints in colorectal cancer

Meta-analysis for the evaluation of surrogate endpoints in cancer clinical trials

“…[74][75][76][77] On the other hand, DFS has demonstrated high validity as a surrogate for OS in adjuvant colon cancer, based on a range of meta-analyses from simple correlation between treatment effects on both endpoints 65,66 to mathematically more sophisticated surrogacy estimation which accounts for trial-and patient-level correlations simultaneously and adjusts for estimation errors of treatment effect on each of the endpoints. 78 In metastatic colorectal cancer, PFS also was demonstrated to achieve strong surrogacy for OS, 75,79 but this did not hold in advanced breast cancer. 77,80 In the setting of prostate cancer, as stated in the recent review paper by Collette et al, 5 "The prostate-specifi c antigen (PSA) is the most studied marker of prostate cancer."…”

Leukemia-free survival as a surrogate end point for overall survival in the evaluation of maintenance therapy for patients with acute myeloid leukemia in complete remission

“…rogate end points has been well established in early-and advanced-stage colorectal cancer. [3][4][5][6] However, the predictive power of a particular surrogate for overall survival is not equivalent for all diseases (e.g. strong in the case of colorectal cancer but weak in the case of advanced breast cancer), [7][8][9] and the use of surrogate end points is not automatically acceptable in all tumor types or stages of disease.…”

“…Other criteria have been proposed in the literature for the validation of surrogate end points, but those adopted here have been used extensively in solid tumors both in the adjuvant treatment and advanced disease settings. [3][4][5]7,13,15,16,23,[31][32][33][34] The trial on which this analysis was based did not achieve significance in its secondary overall survival end point; however, it is noteworthy that the presence or lack of a significant overall survival benefit appears to have little bearing on the success or failure of surrogate validations in solid tumor trials. 3,7 With the available follow-up data in the HDC/IL-2 trial at the time of the database lock, 236 patients had experienced an event contributing to the leukemia-free survival end point (110 in the treatment group and 126 in the control group).…”

“…2 Progression-free survival and disease-free survival in advanced and early-stage colorectal cancer, respectively, are among the best studied, validated, and generally accepted surrogate end points for overall survival. [3][4][5][6] Other time-to-event end points such as time-to-progression or time-to-disease recurrence have been proposed to substitute for overall survival in treatment trials of other solid tumors, including trials investigating breast, [7][8][9] prostate, 10 ovarian, 11 glioblastoma, 12 non-small cell lung, 13,14 head and neck, 15 gastric, 16 and pancreatic 17 cancers. In many circumstances, such end points are in fact more reliable and sensitive indicators of treatment efficacy than overall survival because more events are observed for these end points than for overall survival and they are not confounded by post-progression therapies.…”

Contributions of meta-analyses based on individual patient data to therapeutic progress in colorectal cancer

“…41,47 These results were further validated using data from a meta-analysis conducted by the Meta-Analysis Group of the Japanese Society for Cancer of the Colon and Rectum and the MAGIC. 48 Disease-free survival (DFS) is now the accepted primary endpoint for trials in which the majority of patients have stage III colorectal tumors, and it is therefore important that the defi nition of DFS be standardized. 46 The problem of defi ning an appropriate primary endpoint is more complex in advanced disease because of drug holidays, whereby patients who are in a stable condition can be taken off a drug that has signifi cant cumulative toxicity (such as oxaliplatin).…”