Originally published as JCO Early Release 10.1200/JCO.2008.19.8135 on December 29 2008

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A Randomized Phase IIIB Trial of Chemotherapy, Bevacizumab, and Panitumumab Compared With Chemotherapy and Bevacizumab Alone for Metastatic Colorectal Cancer

From the David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles; Amgen Inc, Thousand Oaks, CA; Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA; M. Zangmeister Center, Columbus, OH; NEA Clinic, Jonesboro, AR; Suburban Hematology-Oncology Associates, Lawrenceville, GA; Sarah Cannon Research Institute, Nashville, TN; Georgetown University Hospital, Washington, DC; Rocky Mountain Cancer Centers, Denver, CO; Baylor-Sammons Cancer Center, Dallas, TX, St. Joseph Mercy Hospital, Ann Arbor, MI.

Corresponding author: J. Randolph Hecht, MD, David Geffen School of Medicine at UCLA, 2825 Santa Monica Blvd, #221, Santa Monica, CA 90404; e-mail: jrhecht{at}mednet.ucla.edu.

Purpose Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC.

Patients and Methods Patients were randomly assigned within each chemotherapy cohort to bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks. The primary end point was progression-free survival (PFS) within the oxaliplatin cohort. Tumor assessments were performed every 12 weeks and reviewed centrally.

Results A total of 823 and 230 patients were randomly assigned to the oxaliplatin and irinotecan cohorts, respectively. Panitumumab was discontinued after a planned interim analysis of 812 oxaliplatin patients showed worse efficacy in the panitumumab arm. In the final analysis, median PFS was 10.0 and 11.4 months for the panitumumab and control arms, respectively (HR, 1.27; 95% CI, 1.06 to 1.52); median survival was 19.4 months and 24.5 months for the panitumumab and control arms, respectively. Grade 3/4 adverse events in the oxaliplatin cohort (panitumumab v control) included skin toxicity (36% v 1%), diarrhea (24% v 13%), infections (19% v 10%), and pulmonary embolism (6% v 4%). Increased toxicity without evidence of improved efficacy was observed in the panitumumab arm of the irinotecan cohort. KRAS analyses showed adverse outcomes for the panitumumab arm in both wild-type and mutant groups.

Conclusion The addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based chemotherapy results in increased toxicity and decreased PFS. These combinations are not recommended for the treatment of mCRC in clinical practice.

Supported by Amgen Inc.

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

Clinical Trials repository link available on www.jco.org.

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