U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
OBJECTIVE
To describe the Food and Drug Administration review and marketing approval considerations for panitumumab (Vectibix) for the third-line treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal carcinoma.


METHODS
Food and Drug Administration reviewed a single, open-label, multicenter trial in which 463 patients with epidermal growth factor receptor-expressing metastatic colorectal cancer who had progressed on or following treatment with a regimen containing a fluoropyrimidine, oxaliplatin, and irinotecan were randomized (1:1) to receive best supportive care (BSC) with or without panitumumab (6 mg/kg every other week) administered until disease progression or intolerable toxicity. Progression and response were confirmed by an independent review committee masked to treatment assignment. At progression, patients in the BSC-alone arm were eligible to receive panitumumab.


RESULTS
Although median progression-free survival (PFS) was similar in both treatment arms ( approximately 8 weeks), the mean PFS was approximately 50% longer among patients receiving panitumumab than among those receiving BSC alone (96 versus 60 days, respectively) and the objective response rate in patients receiving panitumumab was 8%. However, no difference in overall survival was shown between the two study arms.


CONCLUSIONS
Panitumumab received accelerated approval based on improvement in PFS and an independently confirmed response rate of 8%, similar to that observed with other active agents at this advanced stage of disease. Confirmation of clinical benefit will be required for full approval.
Giusti
Ruthann M
RM
Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993-0004, USA. ruthann.giusti@fda.hhs.gov
Shastri
Kaushikkumar
K
Pilaro
Anne M
AM
Fuchs
Chana
C
Cordoba-Rodriguez
Ruth
R
Koti
Kallappa
K
Rothmann
Mark
M
Men
Angela Yuxin
AY
Zhao
Hong
H
Hughes
Monica
M
Keegan
Patricia
P
Weiss
Karen D
KD
Pazdur
Richard
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D017277:Drug Approval; D066246:ErbB Receptors / Q000378:metabolism*; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D015996:Survival Rate; D014481:United States; D014486:United States Food and Drug Administration
D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077544:Panitumumab; D000077146:Irinotecan; D066246:ErbB Receptors; D005472:Fluorouracil; D002166:Camptothecin