Targeting Colorectal Cancer with Anti-epidermal Growth Factor Receptor Antibodies: Focus on Panitumumab

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2010 Jul 10

PMID 20616903

Citations 1

Authors

Kerry J Williams

A Craig Lockhart

Affiliations

Soon will be listed here.

Abstract

The tumor biology targeted therapies have improved outcomes in colorectal cancer (CRC). The epidermal growth factor receptor (EGFR) inhibitors represent one of these successful strategies. EGFR is frequently overexpressed in CRCs and associated with a malignant phenotype. Two EGFR inhibitors have shown efficacy in metastatic CRC, cetuximab and panitumumab. Cetuximab is a human-mouse chimeric monoclonal antibody that binds to the extracellular domain of the EGF-receptor. Similarly, panitumumab is a fully humanized monoclonal IgG(2) antibody, directed against EGFR. Being fully humanized, panitumumab does not contain mouse protein reducing the risk of hypersensitivity. In a pivotal clinical trial, panitumumab was well tolerated and effective, demonstrating an objective response rate of 10% vs best supportive care (ORR = 0%; P < 0.0001). Panitumumab was approved for the treatment of mCRC by the FDA in 2006. Studies combining panitumumab with cytotoxic chemotherapy and other targeted therapies have been completed while others are ongoing to further evaluate the clinical utility of this agent. Recently it has been demonstrated that mutations in KRAS predict the efficacy of panitumumab and cetuximab, limiting their use to CRC patients with wild-type KRAS, and moving the clinical field towards personalized cancer care.

Citing Articles

Patient considerations in metastatic colorectal cancer - role of panitumumab.

Rogers J Onco Targets Ther. 2017; 10:2033-2044.

PMID: 28435294 PMC: 5391168. DOI: 10.2147/OTT.S115430.

References

Locker G, Hamilton S, Harris J, Jessup J, Kemeny N, Macdonald J . ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006; 24(33):5313-27. DOI: 10.1200/JCO.2006.08.2644. View

Weiner L, Belldegrun A, Crawford J, Tolcher A, Lockbaum P, Arends R . Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies. Clin Cancer Res. 2008; 14(2):502-8. DOI: 10.1158/1078-0432.CCR-07-1509. View

Marshall J . Clinical implications of the mechanism of epidermal growth factor receptor inhibitors. Cancer. 2006; 107(6):1207-18. DOI: 10.1002/cncr.22133. View

Andreyev H, Norman A, Cunningham D, Oates J, Clarke P . Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst. 1998; 90(9):675-84. DOI: 10.1093/jnci/90.9.675. View

Bazan V, Migliavacca M, Zanna I, Tubiolo C, Grassi N, Latteri M . Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann Oncol. 2002; 13(9):1438-46. DOI: 10.1093/annonc/mdf226. View

Cohen S, Cohen R, Meropol N . Targeting signal transduction pathways in colorectal cancer--more than skin deep. J Clin Oncol. 2005; 23(23):5374-85. DOI: 10.1200/JCO.2005.02.194. View

De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N . KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol. 2007; 19(3):508-15. DOI: 10.1093/annonc/mdm496. View

Aaronson S . Growth factors and cancer. Science. 1991; 254(5035):1146-53. DOI: 10.1126/science.1659742. View

Ince W, Jubb A, Holden S, Holmgren E, Tobin P, Sridhar M . Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst. 2005; 97(13):981-9. DOI: 10.1093/jnci/dji174. View

10.

Bos J, Fearon E, Hamilton S, Verlaan-de Vries M, VAN Boom J, Van Der Eb A . Prevalence of ras gene mutations in human colorectal cancers. Nature. 1987; 327(6120):293-7. DOI: 10.1038/327293a0. View

11.

Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P . Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26(35):5705-12. DOI: 10.1200/JCO.2008.18.0786. View

12.

Kelly H, Goldberg R . Systemic therapy for metastatic colorectal cancer: current options, current evidence. J Clin Oncol. 2005; 23(20):4553-60. DOI: 10.1200/JCO.2005.17.749. View

13.

Karapetis C, Khambata-Ford S, Jonker D, OCallaghan C, Tu D, Tebbutt N . K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17):1757-65. DOI: 10.1056/NEJMoa0804385. View

14.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

15.

Saltz L, Meropol N, Loehrer Sr P, Needle M, Kopit J, Mayer R . Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004; 22(7):1201-8. DOI: 10.1200/JCO.2004.10.182. View

16.

Esteller M, Gonzalez S, Risques R, Marcuello E, Mangues R, Germa J . K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol. 2001; 19(2):299-304. DOI: 10.1200/JCO.2001.19.2.299. View

17.

Spano J, Lagorce C, Atlan D, Milano G, Domont J, Benamouzig R . Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol. 2004; 16(1):102-8. DOI: 10.1093/annonc/mdi006. View

18.

Rowinsky E, Schwartz G, Gollob J, Thompson J, Vogelzang N, Figlin R . Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol. 2004; 22(15):3003-15. DOI: 10.1200/JCO.2004.11.061. View

19.

Amado R, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman D . Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26(10):1626-34. DOI: 10.1200/JCO.2007.14.7116. View

20.

Mendelsohn J, Baselga J . The EGF receptor family as targets for cancer therapy. Oncogene. 2001; 19(56):6550-65. DOI: 10.1038/sj.onc.1204082. View