open access

Vol 6, No 6 (2010)
Review paper
Published online: 2011-02-24
Get Citation

Panitumumab and inhibition of the epidermal growth factor receptor signaling in the treatment of metastatic colorectal cancer

Lucjan S. Wyrwicz, Zbigniew I. Nowecki
Onkol. Prak. Klin 2010;6(6):290-300.

open access

Vol 6, No 6 (2010)
REVIEW ARTICLES
Published online: 2011-02-24

Abstract

Panitumumab is a human monoclonal antibody that targets epidermal growth factor receptor (EGFR) approved for the treatment of patients with metastatic colorectal cancer (mCRC). The current use of panitumumab is, however, restricted to the management of patients who have failed chemotherapy with irinotecan and oxaliplatin. The results of a phase III studies published in 2010 made it possible to demonstrate clinical benefit from using panitumumab in combination with first- or second-line chemotherapy in mCRC, at the same time confirming in prospective setting the benefits of using anti-EGFR treatments only in the group of patients without the KRAS mutation.
We present the results of these studies and discuss selected communications from ASCO 2010 and WCGI 2010 related to anti-EGFR treatment in mCRC.

Onkol. Prak. Klin. 2010; 6, 6: 290–300

Abstract

Panitumumab is a human monoclonal antibody that targets epidermal growth factor receptor (EGFR) approved for the treatment of patients with metastatic colorectal cancer (mCRC). The current use of panitumumab is, however, restricted to the management of patients who have failed chemotherapy with irinotecan and oxaliplatin. The results of a phase III studies published in 2010 made it possible to demonstrate clinical benefit from using panitumumab in combination with first- or second-line chemotherapy in mCRC, at the same time confirming in prospective setting the benefits of using anti-EGFR treatments only in the group of patients without the KRAS mutation.
We present the results of these studies and discuss selected communications from ASCO 2010 and WCGI 2010 related to anti-EGFR treatment in mCRC.

Onkol. Prak. Klin. 2010; 6, 6: 290–300

Get Citation

Keywords

colorectal cancer; targeted therapy; anti-EGFR treatment; panitumumab

About this article
Title

Panitumumab and inhibition of the epidermal growth factor receptor signaling in the treatment of metastatic colorectal cancer

Journal

Oncology in Clinical Practice

Issue

Vol 6, No 6 (2010)

Article type

Review paper

Pages

290-300

Published online

2011-02-24

Bibliographic record

Onkol. Prak. Klin 2010;6(6):290-300.

Keywords

colorectal cancer
targeted therapy
anti-EGFR treatment
panitumumab

Authors

Lucjan S. Wyrwicz
Zbigniew I. Nowecki

References (61)
  1. Van Cutsem E, Nordlinger B, Cervantes A, et al. ESMO Guidelines Working Group. Advanced colorectal cancer: ESMO Clinical Practice Guidelines for treatment. Ann Oncol. 2010; 21 Suppl 5: v93–v97.
  2. Price TJ, Tebbutt NC, Karapetis CS, et al. Current Opinion on Optimal Treatment Choices in First-line Therapy for Advanced or Metastatic Colorectal Cancer: Report From the Adelaide Colorectal Tumour Group Meeting; Stockholm, Sweden; September 2008. Clin Colorectal Cancer. 2010; 9(1): 8–14.
  3. Gallagher DJ, Kemeny N. Metastatic colorectal cancer: from improved survival to potential cure. Oncology. 2010; 78(3-4): 237–248.
  4. Tol J, Dijkstra JR, Klomp M, et al. Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer. 2010; 46(11): 1997–2009.
  5. Sartore-Bianchi A, Bencardino K, Di Nicolantonio F, et al. Integrated molecular dissection of the epidermal growth factor receptor (EGFR) [corrected] oncogenic pathway to predict response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer. Target Oncol. 2010; 5(1): 19–28.
  6. Lièvre A, Blons H, Laurent-Puig P. Oncogenic mutations as predictive factors in colorectal cancer. Oncogene. 2010; 29(21): 3033–3043.
  7. Fakih MM. KRAS mutation screening in colorectal cancer: From paper to practice. Clin Colorectal Cancer. 2010; 9(1): 22–30.
  8. Tysarowski A, Fabisiewicz A, Kolasa I, et al. Walidacja wybranych technik molekularnych oznaczania mutacji w kodonie 12 i 13 genu K-RAS przeprowadzona w pięciu ośrodkach badawczo-naukowych Polski. Onkol Prakt Klin. 2008; 4: 232–244.
  9. De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010; 11(8): 753–762.
  10. Irahara N, Baba Y, Nosho K, et al. NRAS mutations are rare in colorectal cancer. Diagn Mol Pathol. 2010; 19(3): 157–163.
  11. Sartore-Bianchi A, Bencardino K, Di Nicolantonio F, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26(35): 5705–5712.
  12. Richman S, Seymour M, Chambers P, et al. KRAS and BRAF Mutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial. Journal of Clinical Oncology. 2009; 27(35): 5931–5937.
  13. Fariña-Sarasqueta A, van Lijnschoten G, Moerland E, et al. The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol. 2010; 21(12): 2396–2402.
  14. Bardelli A, Siena S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol. 2010; 28(7): 1254–1261.
  15. Bouchahda M, Karaboué A, Saffroy R, et al. Acquired KRAS mutations during progression of colorectal cancer metastases: possible implications for therapy and prognosis. Cancer Chemother Pharmacol. 2010; 66(3): 605–609.
  16. Morgillo F, Bareschino MA, Bianco R, et al. Primary and acquired resistance to anti-EGFR targeted drugs in cancer therapy. Differentiation. 2007; 75(9): 788–799.
  17. Kaulfuss S, Burfeind P, Gaedcke J, et al. Dual silencing of insulin-like growth factor-I receptor and epidermal growth factor receptor in colorectal cancer cells is associated with decreased proliferation and enhanced apoptosis. Mol Cancer Ther. 2009; 8(4): 821–833.
  18. Qiu LX, Mao C, Zhang J, et al. Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: a meta-analysis of 22 studies. Eur J Cancer. 2010; 46(15): 2781–2787.
  19. Shankaran V, Obel J, Benson AlB. Predicting response to EGFR inhibitors in metastatic colorectal cancer: current practice and future directions. Oncologist. 2010; 15(2): 157–167.
  20. Hecht JR, Mitchell E, Neubauer MA, et al. Lack of correlation between epidermal growth factor receptor status and response to Panitumumab monotherapy in metastatic colorectal cancer. Clin Cancer Res. 2010; 16(7): 2205–2213.
  21. Stephenson JJ, Gregory C, Burris H, et al. An open-label clinical trial evaluating safety and pharmacokinetics of two dosing schedules of panitumumab in patients with solid tumors. Clin Colorectal Cancer. 2009; 8(1): 29–37.
  22. Fracasso PM, Burris H, Arquette MA, et al. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res. 2007; 13(3): 986–993.
  23. Chung CH. Managing premedications and the risk for reactions to infusional monoclonal antibody therapy. Oncologist. 2008; 13(6): 725–732.
  24. Afif W, Loftus EV, Faubion WA, et al. Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease. Am J Gastroenterol. 2010; 105(5): 1133–1139.
  25. Power DG, Shah MA, Asmis TR, et al. Safety and efficacy of panitumumab following cetuximab: retrospective review of the Memorial Sloan-Kettering experience. Invest New Drugs. 2010; 28(3): 353–360.
  26. Nielsen DL, Pfeiffer P, Jensen BV. Six cases of treatment with panitumumab in patients with severe hypersensitivity reactions to cetuximab. Ann Oncol. 2009; 20(4): 798.
  27. Cartwright TH, Genther R. Successful administration of panitumumab alone after severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer. Clin Colorectal Cancer. 2008; 7(3): 202–203.
  28. Lenz HJ. Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events. Oncology (Williston Park). 2006; 20(5 Suppl 2): 5–13.
  29. Lacouture ME, Melosky BL. Cutaneous reactions to anticancer agents targeting the epidermal growth factor receptor: a dermatology-oncology perspective. Skin Therapy Lett. 2007; 12(6): 1–5.
  30. Lacouture ME, Maitland ML, Segaert S, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer. 2010; 18(4): 509–522.
  31. Lacouture ME, Mitchell EP, Piperdi B, et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol. 2010; 28(8): 1351–1357.
  32. Hassel JC, Kripp M, Al-Batran S, et al. Treatment of epidermal growth factor receptor antagonist-induced skin rash: results of a survey among German oncologists. Onkologie. 2010; 33(3): 94–98.
  33. Tejpar S, Piessevaux H, Claes K, et al. Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol. 2007; 8(5): 387–394.
  34. Groenestege WM, Thébault S, van der Wijst J, et al. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest. 2007; 117(8): 2260–2267.
  35. Fakih M. Anti-EGFR monoclonal antibody-induced hypomagnesaemia. Lancet Oncol. 2007; 8(5): 366–367.
  36. Charakterystyka Produktu Leczniczego Vectibix. http://www.ema.europa.eu/docs/pl_PL/document_library/EPAR_-_Product_Information/human/000741/WC500047710. pdf (30.08.2010).
  37. Van Cutsem E, Peeters M, Siena S, et al. 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. 2007; 25(13): 1658–1664.
  38. Giusti RM, Shastri K, Pilaro AM, et al. 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. Clin Cancer Res. 2008; 14(5): 1296–1302.
  39. Van Cutsem E, Siena S, Humblet Y, et al. An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol. 2008; 19(1): 92–98.
  40. eeters M., Price T., Hotko Y. i wsp. Randomized phase 3 study of panitumumab with FOLFIRI vs FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer: Patient reported outcomes (PRO). Prezentacja na ASCO Gastrointestinal Cancers Symposium Orlando, 22-24.01.2010.
  41. Lièvre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008; 26(3): 374–379.
  42. De Roock W, Piessevaux H, De Schutter J, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol. 2008; 19(3): 508–515.
  43. Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26(10): 1626–1634.
  44. Siena S., Cassidy J., Tabernero R.L. i wsp. Randomized phase 3 study of panitumumab with FOLFOX4 compared to FOLFOX4 alone as first-line treatment in patients with metastatic colorectal cancer: the PRIME trial. Prezentacja na ASCO Gastrointestinal Cancers Symposium Orlando, 22-24.01.2010.
  45. Douillard J.Y., Siena S., Cassidy J. i wsp. Randomized phase 3 study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial. Prezentacja ustna na 12 th World Congress on Gastrointestinal Cancer Barcelona, 30.06-03.07.2010.
  46. Bokemeyer C, Bondarenko I, Hartmann JT, et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience. . J. Clin. Oncol. (Meeting Abstracts). 2008; 26: Abstrakt.
  47. Peeters M., Price T., Hotko Y. i wsp. Randomized phase 3 study of panitumumab (pmab) with FOLFIRI compared to FOLFIRI alone as second-line treatment (tx) for metastatic colorectal cancer (mCRC): Secondary endpoint results. Prezentacja ustna na 12 th World Congress on Gastrointestinal Cancer Barcelona, 30.06-03.07.2010.
  48. Shaker A, Lacouture ME, Wu S. Risk of high-grade skin rash in cancer patients treated with panitumumab—A meta-analysis. Journal of Clinical Oncology. 2010; 28(15_suppl): e14079.
  49. Siena S, Cunningham D, et al. Randomized phase III study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial analysis by epidermal growth factor receptor (EGFR) tumor staining. J Clin Oncol. 2010; 28(supl. 15): 3566.
  50. Peeters M, Cervantes-Ruiperez A, Strickland A, et al. Randomized phase III study of panitumumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis by tumor epidermal growth factor receptor (EGFR) staining. J Clin Oncol. 2010; 28(supl. 15): 3565.
  51. , et al Randomized, open-label, phase III study of panitumumab (pmab) with FOLFOX4 versus FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): Efficacy by skin toxicity (ST). J Clin Oncol. 2010; 28(supl. 15): 3528.
  52. Price T, Sobrero AF, Wilson G, et al. Randomized, open-label, phase III study of panitumumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy by skin toxicity (ST). J Clin Oncol. 2010; 28(supl. 15): 3529.
  53. Hofheinz R, Mineur L, Greil R, et al. i 20060314 Study Group. Panitumumab (pmab) with FOLFIRI as first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC): Resections and curative surgery in a phase II single arm, multicenter study (20060314). J Clin Oncol. 2010; 28(supl. 15): Abstrakt.
  54. Hofheinz R., Koehne C.-H., Mineur L. i wsp. Panitumumab with FOLFIRI as first-line treatment of patients with metastatic colorectal cancer: resections and curative surgery in a phase II single-arm, multicenter study (20060314). Prezentacja ustna na ASCO Chicago, 04-08.06.2010.
  55. Carrato A, Gomez A, Escudero MP, et al. Panitumumab plus irinotecan, both given every 3 weeks (Q3W), as second-line treatment for irinotecan-naïve metastatic colorectal cancer (mCRC). J Clin Oncol. 2010; 28(supl. 15): e14025.
  56. Adams R, Meade A, Wasan H, et al. Cetuximab therapy in first-line metastatic colorectal cancer and intermittent palliative chemotherapy: review of the COIN trial. Expert Rev Anticancer Ther. 2008; 8(8): 1237–1245.
  57. Adams RA, Meade AM, Madi A, et al. Toxicity associated with combination oxaliplatin plus fluoropyrimidine with or without cetuximab in the MRC COIN trial experience. Br J Cancer. 2009; 100(2): 251–258.
  58. Van Cutsem E, Nordlinger B, Cervantes A, et al. ESMO Guidelines Working Group. Advanced colorectal cancer: ESMO Clinical Practice Guidelines for treatment. Ann Oncol. 2010; 21 Suppl 5: v93–v97.
  59. Santini D, Loupakis F, Vincenzi B, et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist. 2008; 13(12): 1270–1275.
  60. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010; 28(31): 4697–4705.
  61. Peeters M, Oliner KS, Price TJ, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010; 28(31): 4706–4713.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl