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Regulatory Issues: FDA

FDA Review of a Panitumumab (Vectibix^TM) Clinical Trial for First-Line Treatment of Metastatic Colorectal Cancer

Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

Key Words. Panitumumab • Colorectal cancer • FDA drug review

Correspondence: Ruthann M. Giusti, M.D., U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA. Telephone: 301-796-1359; Fax: 301-796-9845; e-mail: ruthann.giusti{at}fda.hhs.gov

Received November 19, 2008; accepted for publication February 23, 2009; first published online in THE ONCOLOGIST Express on March 12, 2009.

Disclosures: Ruthann M. Giusti: None; Martin H. Cohen: None; Patricia Keegan: None; Richard Pazdur: None

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors or independent peer reviewers.

On September 27, 2006, the U.S. Food and Drug Administration granted accelerated approval to panitumumab (Vectibix^TM; Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor–expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Accelerated approval was based on demonstration of a beneficial effect on progression-free survival (PFS).

The present submission summarizes a second clinical trial, to be included in the panitumumab package insert in June 2008, of chemotherapy and bevacizumab with and without panitumumab in the first-line treatment of patients with metastatic colorectal cancer. The study was closed when inferior PFS and greater toxicity were demonstrated at the time of the planned interim efficacy analysis.

Patients receiving panitumumab in combination with bevacizumab and chemotherapy experienced a higher incidence of death (9% versus 4%) and a higher risk for grade 3 and 4 toxicities than patients receiving bevacizumab and chemotherapy alone. The incidences of any Common Terminology Criteria for Adverse Events grade 3 and 4 adverse events (AEs) were 87% and 72% in the panitumumab and control groups, respectively. Grade 3 and 4 AEs occurring more commonly in panitumumab-treated patients included rash/acneiform dermatitis, diarrhea, dehydration, primarily resulting from diarrhea, hypokalemia, stomatitis/mucositis, and pulmonary embolism.

The addition of panitumumab to bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer was harmful when compared with bevacizumab and chemotherapy alone. The use of panitumumab in this setting cannot be recommended.