Originally published as JCO Early Release 10.1200/JCO.2007.12.0949 on September 17 2007

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Randomized Phase II Trial of Cetuximab, Bevacizumab, and Irinotecan Compared With Cetuximab and Bevacizumab Alone in Irinotecan-Refractory Colorectal Cancer: The BOND-2 Study

Leonard B. Saltz, Heinz-Josef Lenz, Hedy L. Kindler, Howard S. Hochster, Scott Wadler, Paulo M. Hoff, Nancy E. Kemeny, Ellen M. Hollywood, Mithat Gonen, Marcus Quinones, Meroe Morse, Helen X. Chen

From the Department of Biostatistics; Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center; the Department of Medicine, Weill Medical College of Cornell University; Department of Medicine, New York University Cancer Institute, New York, NY; Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Chemotherapy Evaluation Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD

Address reprint requests to Leonard B. Saltz, MD, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Room H-917, New York, NY 10021; e-mail: saltzl{at}MSKCC.ORG

Purpose We evaluated the safety and efficacy of concurrent administration of two monoclonal antibodies, cetuximab and bevacizumab, in patients with metastatic colorectal cancer.

Patients and Methods This was a randomized phase II study in patients with irinotecan-refractory colorectal cancer. All patients were naïve to both bevacizumab and cetuximab. Patients in arm A received irinotecan at the same dose and schedule as last received before study entry, plus cetuximab 400 mg/m² loading dose, then weekly cetuximab 250 mg/m², plus bevacizumab 5 mg/kg administered every other week. Patients in arm B received the same cetuximab and bevacizumab as those in arm A but without irinotecan.

Results Forty-three patients received cetuximab, bevacizumab, and irinotecan (CBI) and 40 patients received cetuximab and bevacizumab alone (CB). Toxicities were as would have been expected from the single agents. For the CBI arm, time to tumor progression (TTP) was 7.3 months and the response rate was 37%; for the CB arm, TTP was 4.9 months and the response rate was 20%. The overall survival for the CBI arm was 14.5 months and the overall survival for the CB-alone arm was 11.4 months.

Conclusion Cetuximab and bevacizumab can be administered concurrently, with a toxicity pattern that seems to be similar to that which would be expected from the two agents alone. This combination plus irinotecan also seems to be feasible. The activity seen with the addition of bevacizumab to cetuximab, or to cetuximab plus irinotecan, seems to be favorable when compared with historical controls of cetuximab or cetuximab/irinotecan in patients who are naïve to bevacizumab.

published online ahead of print at www.jco.org on September 17, 2007.

Supported by the Cancer Therapy Evaluation Program (CTEP) of National Cancer Institute (NCI), under the collaborative agreement between CTEP, Genentech, ImClone, and Bristol-Myers Squibb Co: NCI Grants No. NO1-CM17105, NO1-CM17101, NO1-CM-17102, N01-CM-07003-CM74S, NO1-CM-17003.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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