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Bevacizumab: One Treatment for All the Seasons?

Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy

Susanna Di Segni

Pharmacokinetic Unit, Regina Elena National Cancer Institute, Rome, Italy

Massimo Zeuli, Francesco Cognetti

Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy

To the Editor:

We read with great interest the article by Saltz et al,¹ reporting the results of a randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study, published in the October 10 issue of the Journal of Clinical Oncology.

Forty-three patients affected by irinotecan-refractory colorectal cancer received cetuximab, bevacizumab, and irinotecan (CBI arm) and 40 patients received cetuximab and bevacizumab alone (CB arm).

Although it is not clear from text and Table 1 how many patients received a precise number of prior treatments, I assume that more than 50% received three prior chemotherapy regimens (median number of treatments: three in both arms). However, in the BOND study, less than 50% of patients received (45% and 39% in the two arms, respectively) three prior chemotherapy regimens. I believe that knowing the percentage of the population that had received a precise number of chemotherapy regimens is of crucial importance to quantify the impact of the original schedule in pretreated metastatic colorectal cancer patients. Moreover, such better results in comparison with irinotecan plus cetuximab and cetuximab alone in the BOND study² could lead to a larger magnitude of benefit of introducing bevacizumab in this pretreated population. We cannot understand why the stratification criteria did not include previous treatments with or without prior use of oxaliplatin, which were used for the BOND study.

The second problem arising from this study is the benefit resulting from the addition of bevacizumab to irinotecan plus cetuximab and cetuximab alone. Although comparison between two phase II studies is not methodologically correct, if we consider the BOND study as the historical control, we assume that time to tumor progression is almost doubled or tripled in the two arms by introduction of bevacizumab.

If phase III studies will confirm these preliminary results, could we reasonably defer the introduction of an antiangiogenic agent, or does the expected benefit remains greater when associated with first-line chemotherapy? It will be important also to address (as an ongoing trial is doing) the contribution of bevacizumab after treatment failure from a prior bevacizumab-containing regimen, to realize if this possibility could led to additional improvement of prognosis of these patients.

In conclusion, although BOND-2 is a randomized phase II trial with only 70 patients, important findings were pointed out by the authors, and many other findings have arisen from results; we believe that this trial could modify the treatment of metastatic colorectal cancer, if confirmed by larger randomized phase III trial.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Saltz LB, Lenz HJ, Kindler HL, et al: Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: The BOND-2 study. J Clin Oncol 25:4557-4561, 2007[Abstract/Free Full Text]

2. Cunningham D, Humblet Y, Siena S, et al: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337-345, 2004[Abstract/Free Full Text]

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