|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 25, No 35 (December 10), 2007: pp. 5674 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.5383
In ReplyDuke Comprehensive Cancer Center, Durham, NC
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD
Department of Medical Oncology, Princess Margaret Hospital and University of Toronto, Toronto, Canada
Department of Medical Oncology, Rotterdam Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands Collette et al1 have brought to attention the complexities surrounding validation of surrogate markers in chronic diseases, and we applaud their efforts to establish methodologies that ensure that these markers are considered appropriately. As of 2007, there have been no agents approved by the United States or European regulatory agencies in advanced prostate cancer based on changes in prostate-specific antigen (PSA) or other biomarkers, and to our knowledge, this applies broadly to other malignancies as well. Although mitoxantrone was approved by the US Food and Drug Administration (FDA) based on improved palliation, one could argue that this end point was a true primary end point in itself based on clinical benefit.2 Even though changes in PSA are prognostic across a continuum of declines, the surrogate capabilities of PSA changes in the hormone-refractory state remain unclear and depend on the treatment used.3 Although our point estimates for the degree of surrogacy differed from those of Petrylak et al,4 our results do not exclude the possibility that PSA declines may have adequate surrogacy. However, despite the large size of the TAX327 trial, we did not find strong evidence to support PSA decline as a surrogate end point. We believe that our analysis raises questions as to the degree of surrogacy that is acceptable for clinical and regulatory decision making and for phase II trial end points, and Collette et al appropriately highlight the controversies around the appropriate methodology for determining surrogacy across clinical trials.
Although we recognize that the proportion of treatment effect has important limitations, other measures of surrogacy that have been proposed by Buyse et al5 (for example, the relative effect) do not demonstrate greater degrees of surrogacy than this measure (relative effect = 0.34 in this analysis for the surrogate of AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Ronald de Wit, Sanofi-aventis (C); Mario Eisenberger, Sanofi-aventis (C) Stock Ownership: None Honoraria: Ronald de Wit, Sanofi-aventis; Mario Eisenberger, Sanofi-aventis Research Funding: Ronald de Wit, Sanofi-aventis; Mario Eisenberger, Sanofi-aventis Expert Testimony: None Other Remuneration: Ronald de Wit, Sanofi-aventis; Mario Eisenberger, Sanofi-aventis REFERENCES 1. Collette L, Buyse M, Burzykowski T: Are prostate-specific antigen changes valid surrogates for survival in metastatic hormone-refractory prostate cancer? J Clin Oncol 25:10.1200/JCO.2007.14.5268 2. Tannock IF, Osoba D, Stockler MR, et al: Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: A Canadian randomized trial with palliative endpoints. J Clin Oncol 14:1756-1764, 1996 3. Armstrong AJ, Garrett-Mayer ES, Ou Yang Y, et al: PSA and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol 25:3965-3970, 2007 4. Petrylak DP, Ankerst DP, Jiang CS, et al: Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99-16. J Natl Cancer Inst 98:516-521, 2006 5. Buyse M, Molenberghs G: Criteria for the validation of surrogate endpoints in randomized experiments. Biometrics 54:1014-1029, 1998[CrossRef][Medline] 6. Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004
Related Correspondence
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
30% 3-month PSA decline, with 1 being a perfect surrogate on a 0 to 1 scale). In addition, we believe that the differences in conclusions about surrogate end points between the two prostate studies may reflect the different agents used. We would welcome and support a meta-analysis of individual patient data of docetaxel-treated patients from past clinical trials, but would be concerned that the independent effect of the hormonally active agent estramustine on PSA levels without an independent contribution to survival would simply create heterogeneity in this meta-analysis, further clouding the picture. Given that estramustine is no longer considered a standard first-line treatment regimen in hormone-refractory prostate cancer (HRPC), the relevance of this analysis is questionable. We agree that a meta-analysis would allow a better estimation of individual and trial-level surrogacy. However, one should note that the weekly docetaxel arm had a greater degree of PSA declines, time to progression, and PSA normalization than the every-3-week docetaxel arm, but did not confer a similar survival advantage over mitoxantrone.
