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Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer

Eric Van Cutsem, Marc Peeters, Salvatore Siena, Yves Humblet, Alain Hendlisz, Bart Neyns, Jean-Luc Canon, Jean-Luc Van Laethem, Joan Maurel, Gary Richardson, Michael Wolf, Rafael G. Amado

From the University Hospital Gasthuisberg, Leuven; Ghent University Hospital, Ghent; St Luc University Hospital, Université Catholique de Louvain; Jules Bordet Institute; AZ Vrije Universiteit Brussel; Erasme University Hospital, Brussels; Centre Hospitalier Notre Dame et Reine Fabiola, Charleroi, Belgium; Ospedale Niguarda Cá Granda, Milan, Italy; Hospital Clínic de Barcelona, Barcelona, Spain; Cabrini Hospital, Victoria, Australia; and Amgen Inc, Thousand Oaks, CA

Address reprint requests to Eric Van Cutsem, MD, PhD, Digestive Oncology Unit, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Leuven, Belgium; e-mail: eric.vancutsem{at}uz.kuleuven.ac.be

Purpose: Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR). We compared the activity of panitumumab plus best supportive care (BSC) to that of BSC alone in patients with metastatic colorectal cancer who had progressed after standard chemotherapy.

Patients and Methods: We randomly assigned 463 patients with 1% or more EGFR tumor cell membrane staining, measurable disease, and radiologic documentation of disease progression during or within 6 months of most recent chemotherapy to panitumumab 6 mg/kg every 2 weeks plus BSC (n = 231) or BSC alone (n = 232). Tumor assessments by blinded central review were scheduled from week 8 until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included objective response, overall survival (OS), and safety. BSC patients who progressed could receive panitumumab in a cross-over study.

Results: Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66, [P < .0001]). Median PFS time was 8 weeks (95% CI, 7.9 to 8.4) for panitumumab and 7.3 weeks (95% CI, 7.1 to 7.7) for BSC. Mean (standard error) PFS time was 13.8 (0.8) weeks for panitumumab and 8.5 (0.5) weeks for BSC. Objective response rates also favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P < .0001). No difference was observed in OS (HR, 1.00; 95% CI, 0.82 to 1.22), which was confounded by similar activity of panitumumab after 76% of BSC patients entered the cross-over study. Panitumumab was well tolerated. Skin toxicities, hypomagnesaemia, and diarrhea were the most common toxicities observed. No patients had grade 3/4 infusion reactions.

Conclusion: Panitumumab significantly improved PFS with manageable toxicity in patients with chemorefractory colorectal cancer.

Supported by Amgen Inc, Thousand Oaks, CA.

Presented at the 97th Annual Meeting of the American Association for Cancer Research, April 1-5, 2006, Washington, DC; 2nd Annual Conference of the Hematology/Oncology Pharmacy Association, June 15-18, 2006, Orlando, FL; 8th Annual Conference of the World Congress on Gastrointestinal Cancer, June 28-July 1, 2006, Barcelona, Spain; and at the 31st European Society of Medical Oncology Congress, September 29-October 3, 2006, Istanbul, Turkey.

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

Related Editorial

• Targeted Therapy Trials: Approval Strategies, Target Validation, or Helping Patients?
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  JCO 2007 25: 1639-1641 [Full Text]

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• Targeted Therapies: Cui Prodest?
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