Endpoints and surrogate endpoints in colorectal cancer: A review of recent developments

Current Opinion in Oncology

Volumn 20, Issue 4, 2008, Pages 466-471

  Piedbois, Pascal ^a   Buyse, Marc ^b  

^a HENRI MONDOR HOSPITAL   (France)

^b INTERNATIONAL DRUG DEVELOPMENT INSTITUTE   (Belgium)

Author keywords

Colorectal cancer; Disease free survival; Overall survival; Progression free survival; Surrogate endpoints

Indexed keywords

CARCINOEMBRYONIC ANTIGEN; FLUOROPYRIMIDINE; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; OXALIPLATIN; TUMOR MARKER;

ADVANCED CANCER; CANCER ADJUVANT THERAPY; CANCER GROWTH; CANCER RECURRENCE; CANCER SURGERY; CANCER SURVIVAL; CLINICAL TRIAL; COLON CANCER; COLORECTAL CANCER; DISEASE FREE SURVIVAL; DISEASE SEVERITY; HUMAN; OVERALL SURVIVAL; PATIENT CODING; PREDICTION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REVIEW; THERAPY EFFECT; TUMOR GROWTH; BIOASSAY; CHEMISTRY; COLORECTAL TUMOR; MORTALITY; SURVIVAL RATE;

COLORECTAL NEOPLASMS; ENDPOINT DETERMINATION; HUMANS; SURVIVAL RATE; TUMOR MARKERS, BIOLOGICAL;

EID: 47249152394     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/CCO.0b013e32830218fe     Document Type: Review

References (17)

1. Weir CJ, Walley RJ. Statistical evaluation of biomarkers as surrogate endpoints: a literature review. Stat Med 2006; 25:183-203.
2. Baker SG. A simple meta-analytic approach for using a binary surrogate endpoint to predict the effect of intervention on true endpoint. Biostatistics 2006; 7:58-70.
3. Burzykowski T, Buyse M. Surrogate threshold effect: an alternative measure for meta-analytic surrogate endpoint validation. Pharm Stat 2006; 5:173-186.
4. Locker GY, Hamilton S, Harris J, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 2006; 24:5313-5327.
5. Duffy MJ, van Dalen A, Haglund C, et al. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer 2007; 43:1348-1360.
6. Tournigand C, Cervantes A, Figer A, et al. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer: a GERCOR study. J Clin Oncol 2006; 24:394-400.
7. Allegra C, Blanke C, Buyse M, et al. End points in advanced colon cancer clinical trials: a review and proposal. J Clin Oncol 2007; 25:3572-3575. The authors review the main endpoints in ACC and propose a new composite endpoint that takes into account the complexity of the management of these patients, including possible therapeutic windows.
8. Johnson KR, Ringland C, Stokes BJ, et al. Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or nonsmall-cell lung cancer: a meta-analysis. Lancet Oncol 2006; 9:741-746.
9. Golfinopoulos V, Salanti G, Pavlidis N, Ioannidis JP. Survival and disease-progression benefits with treatment regimens for advanced colorectal cancer: a meta-analysis. Lancet Oncol 2007; 8:898-911. In this study, the authors present a meta-analysis of 37 trials performed in ACC in an attempt to identify the most active regimens. Analyses are based on published data.
10. Tang PA, Bentzen SM, Chen EX, Siu LL. Surrogate end points for median overall survival in metastatic colorectal cancer: literature-based analysis from 39 randomized controlled trials of first-line chemotherapy. J Clin Oncol 2007; 25:4562-4568. Correlations between ORR, TTP, PFS and OS are explored in a set of 39 publications on randomized clinical trials in ACC. A strong correlation between PFS and OS is reported in this literature-based study. The authors estimate that the risk reduction for OS is about half the risk reduction for PFS.
11. Buyse M, Burzykowski T, Carroll K, et al. Progression-free survival is a surrogate for survival in advanced colorectal cancer. J Clin Oncol 2007; 25:5218-5224. IPD from 10 historical and three validation trials are used to confirm that PFS is a surrogate for OS in ACC. In this study, PFS and OS over the entire time range are well correlated, with a rank correlation coefficient of 0.82. The PFS and OS hazard ratios are also well correlated, with a correlation coefficient of 0.99. In this model, a PFS hazard ratio of 0.77 or lower predicts a benefit in terms of OS.
12. Punt CJ, Buyse M, Köhne CH, et al. Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst 2007; 99:998-1003. An overview of the literature on endpoints used in early disease, and a proposal for standardization of these endpoints.
13. Sargent DJ, Wieand HS, Haller DG, et al. 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. J Clin Oncol 2005; 23:8664-8670.
14. Yothers G. Toward progression free survival as a primary end point in advanced colorectal cancer. J Clin Oncol 2007; 25:5153-5154.
15. Braun MS, Quirke P, Seymour MT. Molecular markers of chemotherapeutic response and toxicity in colorectal cancer. Expert Rev Anticancer Ther 2007; 7:489-501.
16. Gupta M. Circulating endothelial cells and circulating endothelial cell progenitors as surrogate markers for determining response to antiangiogenic agents. Clin Colorectal Cancer 2007; 6:337-338.
17. Vincenzi B, Santini D, Russo A, et al. Circulating VEGF reduction, response and outcome in advanced colorectal cancer patients treated with cetuximab plus irinotecan. Pharmacogenomics 2007; 8:319-327. Conclusion The last couple of years have seen intensive attempts to better define and extendthe endpoints currently used in both early CRC and ACC. New statistical methodologyhas been developed to validate SEPs by examining the correlation between the surrogate and the true endpoint and between the treatment effects on these endpoints. DFS and PFS have been shown to be acceptable surrogates for OS, respectively to assess new adjuvant treatments and first-line treatments for advanced disease. These efforts should be pursued in the coming years in order to identify biomarkers that could be used as valid SEPs for long-term clinical endpoints such as DFS, PFS, or OS.