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In Reply

Matti S. Aapro

IMO Clinique de Genolier, Genolier, Switzerland

We appreciate the possibility to reply to the comment by Codacci-Pisanelli et al regarding the interpretation of the results of our prospective randomized study.¹ They suggest additional analyses of survival data at similar time points as used in the Leyland-Jones et al² study. We agree with the comment that the results of the Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study require cautious interpretation. The results do not indicate differences in overall survival, but the study was not designed to formally exclude such differences.

With regard to analyses at different time points, we would like to reiterate that the primary efficacy outcome was a comparison of overall survival between treatment groups. The prespecified primary study end point was an analysis after the last patient had completed her 18-month follow-up period, and the results do not indicate any differences between the two study groups, in contrast to the BEST study by Leyland-Jones et al.²

Analyses defined post hoc based on time points defined by visual inspection of the Kaplan-Meier curve risk inflating type I errors and introducing serious bias. Therefore, such analyses have to be interpreted with even more caution.

After the complete publication of the BEST study,² two post hoc analyses on survival were performed at time points (4 and 12 months) similar to those presented in the BEST study. Consistent with the analysis of the primary study end point of the BRAVE study, there were no significant differences in survival when analyzing the data at these two time points (4 months: event rate, 15.3% in the epoetin beta group and 13.4% in the control group [log-rank P = .54]; 12 months: event rate, 41.9% in the epoetin beta group and 41.9% in the control group [log-rank test P = .73], respectively). We thank our colleagues for this opportunity to indicate that no differences between the study groups have been observed when tailoring survival analyses to end points of 4 and 12 months.

AUTHOR'S 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: Matti S. Aapro, Roche (C) Stock Ownership: None Honoraria: None Research Funding: Matti S. Aapro, Roche (C) Expert Testimony: None Other Remuneration: None

ACKNOWLEDGMENTS

Dr. Aapr is writing on behalf of the BRAVE Steering Committee and Investigators.

NOTES

published online ahead of print at www.jco.org on April 28, 2008

REFERENCES

1. Aapro M, Leonard RC, Barnadas A, et al: Effect of once-weekly epoetin beta on survival in patients with metastatic breast cancer patients receiving anthracycline-and/or taxane-based chemotherapy: Results of the Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study. J Clin Oncol 26:592-598, 2008[Abstract/Free Full Text]

2. Leyland-Jones B, Semiglazov V, Pawlicki M, et al: Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: A survival study. J Clin Oncol 23:5960-5972, 2005[Abstract/Free Full Text]

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