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Drug Insight: panitumumab, a human EGFR-targeted monoclonal antibody with promising clinical activity in colorectal cancer

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Despite the progress achieved with the introduction of new cytotoxic agents, CRC recurrence rates for patients with resected stage II and/or stage III disease remain higher than 20%. Furthermore, for patients diagnosed with metastatic CRC, the median survival time remains below 2 years and cure is often an elusive goal. These data highlight the need for more-effective systemic therapies. The EGFR is frequently overexpressed in CRC and has been associated with the malignant phenotype. Numerous clinical trials are now investigating the role of EGFR-targeted agents in CRC and have produced some encouraging results. Panitumumab is a fully human IgG2 monoclonal antibody that in a randomized phase III trial was shown to increase efficacy when added to best supportive care in patients with chemotherapy-refractory metastatic CRC. In phase I–III trials, panitumumab was safe and well tolerated, with most of its adverse effects related to some form of skin toxic effect. Early studies assessing the safety and efficacy of panitumumab alongside chemotherapy have also yielded promising results, and this combination is now being investigated in the first-line and second-line settings in randomized clinical trials.

Key Points

  • EGFR is frequently overexpressed in colorectal cancer (CRC) and is associated with the malignant phenotype

  • EGFR is a promising treatment target in CRC

  • Panitumumab is a high affinity, fully human IgG2 monoclonal antibody with proven clinical activity in metastatic CRC

  • Panitumumab is active in metastatic CRC as a single agent or in combination with chemotherapy, regardless of the level of EGFR expression in the tumor

  • In a phase III trial, panitumumab almost halved the risk of disease progression as compared with best supportive care alone after failure of standard chemotherapy

  • Panitumumab is generally well tolerated by patients, with most of its adverse effects related to some form of skin reaction

  • Predictive markers of response to EGFR-targeted therapy are currently under investigation

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References

  1. Douillard JY et al. (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355: 1041–1047

    Article  CAS  PubMed  Google Scholar 

  2. de Gramont A et al. (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18: 2938–2947

    Article  CAS  PubMed  Google Scholar 

  3. Twelves C et al. (2002) Capecitabine as first-line treatment in colorectal cancer: pooled data from two large, phase III trials. Eur J Cancer 38 (Suppl 2): S15–S20

    Article  CAS  Google Scholar 

  4. Twelves C et al. (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352: 2696–2704

    Article  CAS  PubMed  Google Scholar 

  5. de Gramont A et al. (2005) Oxaliplatin/5FU/LV in the adjuvant treatment of stage III colon cancer: efficacy results with a median follow-up of 4 years [abstract #3501]. J Clin Oncol 23: a16S

    Article  Google Scholar 

  6. Wolmark N et al. (2005) A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: results of NSABP Protocol C-07 [abstract #3500]. J Clin Oncol 23: a16S

    Article  Google Scholar 

  7. Landis SH et al. (1999) Cancer statistics, 1999. CA Cancer J Clin 49: 8–31

    Article  CAS  PubMed  Google Scholar 

  8. Tournigand C et al. (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22: 229–237

    Article  CAS  PubMed  Google Scholar 

  9. Colucci G et al. (2005) Gruppo Oncologico Dell'Italia Meridionale: phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol 23: 4866–4875

    Article  CAS  PubMed  Google Scholar 

  10. Hurwitz H et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342

    Article  CAS  PubMed  Google Scholar 

  11. Saltz L et al. (2007) Bevacizumab (Bev) in combination with XELOX or FOLFOX4: updated efficacy results from XELOX-1/ NO16966, a randomized phase III trial in first-line metastatic colorectal cancer [abstract #4028]. J Clin Oncol 25: a18S

    Google Scholar 

  12. Porebska I et al. (2000) Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERBB2, ERBB3) in colorectal adenocarcinomas and adenomas. Tumour Biol 21: 105–115

    Article  CAS  PubMed  Google Scholar 

  13. Spano JP et al. (2005) Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives. Ann Oncol 16: 189–194

    Article  CAS  PubMed  Google Scholar 

  14. Carpenter G and Cohen S (1990) Epidermal growth factor. J Biol Chem 265: 7709–7712

    CAS  PubMed  Google Scholar 

  15. Hemming AW et al. (1992) Prognostic markers of colorectal cancer: an evaluation of DNA content, epidermal growth factor receptor, and Ki-67. J Surg Oncol 51: 147–152

    Article  CAS  PubMed  Google Scholar 

  16. Mayer A et al. (1993) The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer 71: 2454–2460

    Article  CAS  PubMed  Google Scholar 

  17. Aaronson SA (1991) Growth factors and cancer. Science 254: 1146–1153

    Article  CAS  PubMed  Google Scholar 

  18. Ciardiello F and Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7: 2958–2970

    CAS  PubMed  Google Scholar 

  19. Sako Y et al. (2000) Single-molecule imaging of EGFR signalling on the surface of living cells. Nat Cell Biol 2: 168–172

    Article  CAS  PubMed  Google Scholar 

  20. Spano JP et al. (2005) Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 16: 102–108

    Article  PubMed  Google Scholar 

  21. McKay JA et al. (2002) Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumors and lymph node metastases. Eur J Cancer 38: 2258–2264

    Article  CAS  PubMed  Google Scholar 

  22. Yang XD et al. (1999) Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res 59: 1236–1243

    CAS  PubMed  Google Scholar 

  23. Yang XD et al. (2001) Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 38: 17–23

    Article  CAS  PubMed  Google Scholar 

  24. Foon KA et al. (2004) Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 58: 984–990

    Article  CAS  PubMed  Google Scholar 

  25. Lynch DH and Yang XD (2002) Therapeutic potential of ABX-EGF: a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment. Semin Oncol 29 (Suppl 4): S47–S50

    Article  Google Scholar 

  26. Jia XC et al. (2000) Inhibition of vascular endothelial cell growth factor and interleukin-8 production in tumor and endothelial cell lines by a fully human monoclonal antibody to epidermal growth factor receptor [abstract #290]. Cancer Res

  27. Yang XD et al. (2000) Inhibition of human cancer growth by ABX-EGF, a fully human anti-EGF receptor monoclonal antibody [abstract #530]. Cancer Res

  28. Iannello A and Ahmad A (2005) Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev 24: 487–499

    Article  CAS  PubMed  Google Scholar 

  29. Figlin RA et al. (2002) ABX-EGF, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with advanced cancer: phase 1 clinical results [abstract #35]. Proc Am Soc Clin Oncol 21: 10a

    Google Scholar 

  30. Roskos L et al. (2002) Low pharmacokinetic variability facilitates optimal dosing of ABX-EGF in cancer patients [abstract #362]. Proc Am Soc Clin Oncol 21

  31. Cunningham D et al. (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351: 337–345

    Article  CAS  PubMed  Google Scholar 

  32. Arends R et al. (2005) Flexible dosing schedules of panitumumab (ABX-EGF) in cancer patients [abstract #3089]. J Clin Oncol 23: a16S

    Article  Google Scholar 

  33. Weiner LM et al. (2005) Updated results from a dose and schedule study of panitumumab (ABX-EGF) monotherapy, in patients with advanced solid malignancies [abstract #3059]. J Clin Oncol 23: a16S

    Article  Google Scholar 

  34. Stephenson J et al. (2007) Administration of panitumumab (Pmab) as a 30-min or 60-min infusion: Safety and pharmacokinetics (PK) from a phase 1 study in patients (pts) with solid tumors [abstract #368]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  35. Yamada Y et al. (2007) Safety and pharmacokinetics (PK) of panitumumab in Japanese patients (pts) with advanced solid malignancies [abstract #385]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  36. Malik I et al. (2005) Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC) [abstract #3520]. J Clin Oncol 23: a16S

    Google Scholar 

  37. Berlin J et al. (2006) Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing ≥ 10% epidermal growth factor receptor (EGFr) [abstract #3548]. J Clin Oncol 24: a18S

    Article  Google Scholar 

  38. Hecht JR et al. (2007) Panitumumab activity in metastatic colorectal cancer (mCRC) patients (pts) with low or negative tumor epidermal growth factor receptor (EGFr) levels: an updated analysis [abstract #350]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  39. Hecht J et al. (2006) Panitumumab in combination with 5-fluorouracil, leucovorin, and irinotecan (IFL) or FOLFIRI for first-line treatment of metastatic colorectal cancer (mCRC) [abstract # 237]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  40. Saltz LB et al. (2005) Interim report of randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer [abstract #169b]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  41. Schwartzberg L et al. (2007) Safety and pharmacokinetics (PK) of AMG 706 with panitumumab plus FOLFIRI or FOLFOX for the treatment of patients (pts) with metastatic colorectal cancer (mCRC) [abstract #4081]. J Clin Oncol 25: a18S

    Google Scholar 

  42. Hecht J et al. (2007) An interim analysis of efficacy and safety from a randomised controlled trial of panitumumab with chemotherapy plus bevacizumab (BEV) in metastatic colorectal cancer (MCRC) [abstract #O-0033]. Ann Oncol 18 (Suppl 7): aSvii21

    Google Scholar 

  43. Van Cutsem E et al. (2007) 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. J Clin Oncol 25: 1658–1664

    Article  CAS  PubMed  Google Scholar 

  44. Peeters M et al. (2007) Efficacy and safety of panitumumab across five clinical studies in patients (pts) with metastatic colorectal cancer (mCRC) [abstract #336]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  45. Hecht RJ et al. (2006) Safety and tolerability of panitumumab, a fully human monoclonal antibody (Mab), in patients with metastatic colorectal cancer (mCRC). Ann Oncol 17 (Suppl 9): 124

    Google Scholar 

  46. Giusti RM et al. (2007) FDA Drug Approval Summary: panitumumab (Vectibix). Oncologist 12: 577–583

    Article  CAS  PubMed  Google Scholar 

  47. Segaert S and Van Cutsem E (2005) Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 16: 1425–1433

    Article  CAS  PubMed  Google Scholar 

  48. Hendlisz A et al. (2006) Treatment effect with panitumumab by skin toxicity: results from a phase 3 trial. Ann Oncol 17 (Suppl 9): 284

    Google Scholar 

  49. Humblet Y et al. (2007) Association of skin toxicity (ST) severity with clinical outcomes and health-related quality of life (HRQoL) with panitumumab (Pmab) [abstract #4038]. J Clin Oncol 25: a18S

    Google Scholar 

  50. Van Cutsem E et al. (2007) A phase III randomized controlled trial of panitumumab (Pmab) in patients (pts) with metastatic colorectal cancer (mCRC): Subset analyses in elderly pts and in pts with poor performance status [abstract #349]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  51. Tejpar S et al. (2007) Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol 8: 387–394

    Article  CAS  PubMed  Google Scholar 

  52. Helbling D and Borner M (2007) Successful challenge with the fully human EGFR antibody panitumumab following an infusion reaction with the chimeric EGFR antibody cetuximab. Ann Oncol 18: 963–964

    Article  CAS  PubMed  Google Scholar 

  53. Langerak A et al. (2007) Institutional experiences with panitumumab monotherapy in metastatic colorectal cancer (mCRC) patients (pts) intolerant to cetuximab. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007. 14579

    Google Scholar 

  54. ERBITUX (Cetuximab) label details [http://www.fda.gov/cder/foi/label/2004/125084lbl.pdf]

  55. Hotta K et al. (2005) Interstitial lung disease in Japanese patients with non-small cell lung cancer receiving gefitinib: an analysis of risk factors and treatment outcomes in Okayama Lung Cancer Study Group. Cancer J 11: 417–424

    Article  CAS  PubMed  Google Scholar 

  56. Amgen discontinues Vectibix(TM) treatment in PACCE trial evaluating Vectibix(TM) as part of triple combination regimen (2007). Press release 22/03/07 [http://www.ext.amgen.com/media/media_pr_detail.jsp?year=2007&releaseID =977186]

  57. Saltz LB et al. (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22: 1201–1208

    Article  CAS  PubMed  Google Scholar 

  58. Saltz L (2005) Epidermal growth factor receptor-negative colorectal cancer: is there truly such an entity? Clin Colorectal Cancer 5 (Suppl 2): S98–S100

    Article  CAS  PubMed  Google Scholar 

  59. Chung KY et al. (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23: 1803–1810

    Article  CAS  PubMed  Google Scholar 

  60. Hebbar M et al. (2006) Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer. Anticancer Drugs 17: 855–857

    Article  CAS  PubMed  Google Scholar 

  61. Lenz HJ et al. (2006) Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 24: 4914–4921

    Article  CAS  PubMed  Google Scholar 

  62. Van Cutsem E et al. (2007) Cetuximab dose-escalation study in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): pharmacokinetic and efficacy data of a randomized study [abstract #237]. Gastrointestinal Cancers Symposium: 2007, January 19–21: Orlando

    Google Scholar 

  63. Cappuzzo F et al. (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 97: 643–655

    Article  CAS  PubMed  Google Scholar 

  64. Takano T et al. (2005) Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 23: 6829–6837

    Article  CAS  PubMed  Google Scholar 

  65. Moroni M et al. (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6: 279–286

    Article  CAS  PubMed  Google Scholar 

  66. Lievre A et al. (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66: 3992–3995

    Article  CAS  PubMed  Google Scholar 

  67. Vallbohmer D et al. (2005) Molecular determinants of cetuximab efficacy. J Clin Oncol 23: 3536–3544

    Article  PubMed  Google Scholar 

  68. Vincenzi B et al. (2006) New issues on cetuximab mechanism of action in epidermal growth factor receptor-negative colorectal cancer: the role of vascular endothelial growth factor. J Clin Oncol 24: 1957

    Article  PubMed  Google Scholar 

  69. Eberhard DA et al. (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23: 5900–5909

    Article  CAS  PubMed  Google Scholar 

  70. Lynch TJ et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350: 2129–2139

    Article  CAS  PubMed  Google Scholar 

  71. De Roock W et al. (2007) KRAS mutations preclude tumor shrinkage of colorectal cancers treated with cetuximab [abstract #4132]. Proc Am Soc Clin Oncol 25: a18s

    Google Scholar 

  72. Shia J et al. (2005) Epidermal growth factor receptor expression and gene amplification in colorectal carcinoma: an immunohistochemical and chromogenic in situ hybridization study. Mod Pathol 18: 1350–1356

    Article  CAS  PubMed  Google Scholar 

  73. Garufi C et al. (2006) Epidermal growth factor gene amplification is not frequent and cannot account for antitumor activity of cetuximab plus chemotherapy in advanced colorectal cancer patients. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement) 3561

    Google Scholar 

  74. Sauer T et al. (2005) Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy? Histopathology 47: 560–564

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Yves Humblet.

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Y Humblet declared he is a Consultant and has been on the Speakers bureau for Amgen. He also received grant and research support from Amgen. M Mano declared no competing interests.

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Mano, M., Humblet, Y. Drug Insight: panitumumab, a human EGFR-targeted monoclonal antibody with promising clinical activity in colorectal cancer. Nat Rev Clin Oncol 5, 415–425 (2008). https://doi.org/10.1038/ncponc1136

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