A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer.

Abstract

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.

• Authors: J Randolph Hecht, Edith Mitchell, Tarek Chidiac, Carroll Scroggin, Christopher Hagenstad, David Spigel, John Marshall, Allen Cohn, David McCollum, Philip Stella, Robert Deeter, Seta Shahin, Rafael G Amado
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 5 Pg. 672-80 (Feb 10 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19114685 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Organoplatinum Compounds
• Oxaliplatin
• Bevacizumab
• Panitumumab
• Irinotecan
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Bevacizumab
• Camptothecin (administration & dosage, analogs & derivatives)
• Colorectal Neoplasms (drug therapy, mortality)
• Female
• Humans
• Irinotecan
• Male
• Middle Aged
• Neoplasm Metastasis
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Panitumumab