PMID- 19282350 OWN - NLM STAT- MEDLINE DCOM- 20090716 LR - 20181201 IS - 1549-490X (Electronic) IS - 1083-7159 (Linking) VI - 14 IP - 3 DP - 2009 Mar TI - FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. PG - 284-90 LID - 10.1634/theoncologist.2008-0254 [doi] AB - On September 27, 2006, the U.S. Food and Drug Administration granted accelerated approval to panitumumab (Vectibix; 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. FAU - Giusti, Ruthann M AU - Giusti RM AD - Office of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA. ruthann.giusti@fda.hhs.gov FAU - Cohen, Martin H AU - Cohen MH FAU - Keegan, Patricia AU - Keegan P FAU - Pazdur, Richard AU - Pazdur R LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20090312 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Organoplatinum Compounds) RN - 04ZR38536J (Oxaliplatin) RN - 2S9ZZM9Q9V (Bevacizumab) RN - 6A901E312A (Panitumumab) RN - 7673326042 (Irinotecan) RN - U3P01618RT (Fluorouracil) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Bevacizumab MH - Camptothecin/administration & dosage/adverse effects/analogs & derivatives MH - Colorectal Neoplasms/*drug therapy/pathology MH - Disease-Free Survival MH - Drug Approval MH - Female MH - Fluorouracil/administration & dosage/adverse effects MH - Humans MH - Irinotecan MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Organoplatinum Compounds/administration & dosage/adverse effects MH - Oxaliplatin MH - Panitumumab MH - Treatment Outcome MH - United States MH - United States Food and Drug Administration EDAT- 2009/03/14 09:00 MHDA- 2009/07/17 09:00 CRDT- 2009/03/14 09:00 PHST- 2009/03/14 09:00 [entrez] PHST- 2009/03/14 09:00 [pubmed] PHST- 2009/07/17 09:00 [medline] AID - theoncologist.2008-0254 [pii] AID - 10.1634/theoncologist.2008-0254 [doi] PST - ppublish SO - Oncologist. 2009 Mar;14(3):284-90. doi: 10.1634/theoncologist.2008-0254. Epub 2009 Mar 12.