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PACS 01 Trial: Questions About Patients' Characteristics and Reported Results

European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium

To the Editor:

We read the PACS 01 trial article published by Roché et al¹ with interest and have three questions regarding the results. It is important to have the right understanding of the estimates that were obtained in this influential trial, especially in view of the first comment below.

Our first question is related to the distribution of baseline characteristics. We noticed that there is some degree of imbalance between treatment arms for several patients' characteristics: notably, 47 more patients having T1 tumors in the FEC-D arm (fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel), 34 more patients with T2 tumors in the FEC arm (fluorouracil, epirubicin, and cyclophosphamide), 24 extra patients with grade 1 tumors in the FEC-D arm, 58 more patients with estrogen receptor–positive tumors in the FEC-D arm, and 30 more patients with hormone receptor–negative tumors in the FEC arm. In addition, there is a difference in the number of patients according to the number of positive lymph nodes (with a surplus of 15 patients in the 1 to 3 positive lymph node category in the FEC-D arm). Considering that the number of lymph nodes was a stratification factor, one would not expect such a difference. Unfortunately, each one of these imbalances can be interpreted as being in favor of the FEC-D arm because of better prognosis. As a consequence, our concern is that the primary analysis (both unadjusted and adjusted for stratification factors) of disease-free survival (DFS) is suffering from bias and cannot be taken at face value.

The second question is related to the P value for the nonadjusted analysis of DFS. In the abstract and in the text, it is written that the P value is .011, with no accompanying hazard ratio (HR) or CI reported. However, if we make a calculation from the numbers provided in Figure 1B (HR = 0.83; CI, 0.69 to 0.99), we find an approximate P value of .043 for DFS. We are unable to explain this apparent difference.

And the third comment is that we fail to understand why the HR obtained with the adjusted analysis (0.82; Table 3) is lower than the one obtained without adjustment (0.83; Fig 1B). Since several important patients' characteristics have more patients with good prognosis in the FEC-D arm than in the FEC arm, we would have expected the adjusted HR to be closer to 1 than the nonadjusted one. We believe this unexpected result requires further explanation.

Due to the importance of this trial, we would be very grateful if the authors could provide an answer to these items, so as to clarify any possible misunderstanding.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCE

1. Roché H, Fumoleau P, Spielmann M, et al: Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: The FNCLCC PACS 01 Trial. J Clin Oncol 24: 5664-5671, 2006[Abstract/Free Full Text]

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