Cetuximab in treatment of metastatic colorectal cancer: background and clinical observation
https://doi.org/10.21518/2079-701X-2018-19-32-41
Abstract
Today, the researchers continue the search for the most optimal regimens of drug therapy for metastatic colorectal cancer (mCRC) which are supposed to increase progression-free survival (PFS) and overall survival (OS), improve patient quality of life. Due to significant progress in chemotherapy (CT) and surgical treatment of mCRC, and the multidisciplinary approach, the treatment algorithms have changed. The increase in life expectancy of patients is observed when all three of the most active chemotherapy drugs in this disease: oxaliplatin (Oxa), irinotecan (Iri), fluoropyrimidines are administered. The inclusion of the targeted drug cetuximab in modern mCRC treatment regimens led to a statistically significant increase in the objective response rate (ORR), median PFS and OS. The article presents the results of the most significant clinical studies of the eficacy of the antiEGFR drug cetuximab in combination with standard CT regimens for the first- and second-line treatment of mCRC, and describes a clinical case of the successful use of cetuximab in mCRC therapy.
About the Authors
A. D. DarenskayaRussian Federation
N. V. Dobrova
Russian Federation
B. M. Medvedeva
Russian Federation
References
1. Goldstein N et al. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res, 1995, 1: 1311-1318.
2. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res. 2001, 7: 2958–2970.
3. Arteaga C. The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J. Clin. Oncol., 2001, 19(Suppl. 18): 32S-40S.
4. Lenz H-J. Cetuximab in the management of colorectal cancer. Biol Targ Ther, 2007, 1(2): 77–91.
5. Mendelsohn J et al. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J. Clin. Oncol. 2003, 21: 2787-2799.
6. Moosmann N, Heinemann V. Cetuximab in the treatment of metastatic colorectal cancer. Exp Opin Biol Ther, 2007, 7(2): 243–256.
7. Vallbohmer D et al. Molecular determinants of cetuximab efficacy. J. Clin. Oncol., 2005, 23: 3536-3544.
8. Vincenzi B et al. Angiogenesis modifications related with cetuximab plus irinotecan as anticancer treatment in advanced colorectal cancer patients. Ann. Oncol., 2006, 17: 835-841.
9. Cunningham D et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinitecanrefractory metastatic colorectal cancer. N. Engl. J. Med., 2004, 351(4): 337-345.
10. Sobrero AF et al. EPIC: Phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J. Clin. Oncol., 2008, 26(14).
11. Komatsu Y et al. Phase II trial of irinotecan plus s-1 (IRIS) with cetuximab (IRIS/Cet) as second-line treatment in patients with KRAS wild-type metastatic colorectal cancer (mCRC): HGCSG0902—Comparison of administration interval in cetuximab treatment. J. Clin. Oncol. (Meeting Abstracts), 2015, 33(Suppl. 3): 746 p.
12. Diaz-Rubio E et al. Cetuximab in combination with oxaliplatin|5-fluorouracil(5-FU)/folinic acid (Fa) (FOLFOX-4) in first-line treatment of patients with epidermal growth factor receptor (EGFR) – expressing metastatic colorectal cancer: An intenational phase 2 study. Proc Am Soc Clin Oncol, 2005, abstr. 3535.
13. Van Cutsem E et al. An international phase II study of cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with metastatic colorectal cancer (CRC) expressing Epidermal Growth Factor Receptor (EGFR). Ann Oncol, 2004, 15(Suppl. 3): abstr. 339P.
14. Seufferlein T, Dittrich C et al. A phase I/II study of cetuximab with 5-fluorouracil plus weekly oxliplatin in first – line treatment of patients with metastatic colorectal cancer expressing epidermal growth factor receptor. ASCO, 2005, abstr. 3644.
15. Borner M, Mingrone W, Koeberle D et al. The impact of cetuximab on the capecitabine plus oxaliplatin (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC): A randomized phase II trial of the Swiss Group for Clinical Cancer Research (SAKK) Proc. ASCO, 2006, 3551.
16. Tabernero J, Van Cutsem E, Diaz-Rubio E et al. Phase II Trial of Cetuximab in Combination With Fluorouracil, Leucovorin, and Oxaliplatin in the First-Line Treatment of Metastatic Colorectal Cancer. J Clin Oncol, 2007, 25: 5225– 5232.
17. Tveit K, Guren T, Glimelius B et al. Randomized phase III study of 5-flurouracil/folinate/oxaliplatin given continuously or intermittently with or without cetuximab, as first-line therapy of metastatic colorectal cancer: the NORDIC VII study (NCT0014314), by the Nordic Colorectal Cancer Biomodulation Group. J Clin Oncol, 2011, 29(Suppl. 4): abstr. 365.
18. Van Cutsem E, Nowacki M et al. Randomized phase III study of irinotecan and 5FU/FA with or without cetuximab in the first-line treatment of pts with metastatic colorectal cancer. CRYSTAL trial. ASCO, 2007, abstr. 4000.
19. Van Cutsem E, Nowacki M, Lang I et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the firstline treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial. Journal of Clinical Oncology, 2007, 25(Suppl. 18): 164S.
20. Bokemeyer C et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol., 2009, 27(5): 663-671.
21. 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: 508–515.
22. Di Fiore F, Blanchard F, Charbonnier F et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer, 2007, 96: 1166–1169.
23. Lievre 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: 374– 379.
24. Custodio A, Feliu J. Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: beyond KRAS mutations. Critic Rev Oncol Hematol, 2013, 85: 45–81.
25. Gorbunova VA. The need for an in-depth analysis of RAS mutations to develop therapeutic strategy for colorectal cancer. Onkologicheskaya Koloproktologia, 2014, 1: 7-13.
26. Semenov NN. High activity of Vectibix in patients with wild-type RAS mCRC. Onkologicheskaya Koloproktologia, 2014, 2: 18–21.
27. Lambrechts D. The role of KRAS, BRAF, NRAS, and PIK3CA mutations as markers of resistance to cetuximab in chemorefractory metastatic colorectal cancer. J. Clin. Oncol. (Meeting Abstracts), 2009, 27(15S): 4020 p.
28. De Roock W et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy ofcetuximab plus chemotherapy in chemotherapyrefractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol, 2010, 11(8): 753-762.
29. 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.
30. Douillard JY, Oliner KS, Siena S et al. Panitumumab FOLFOX-4 treatment and RAS mutations in colorectal cancer. N Engl J Med, 2013, 369: 1023–1034.
31. Moosmann N, von Weikersthal LF, VehlingKaiser U et al. Final analysis of the randomized trial of the German AIO CRC study group: Cetuximab plus XELIRI versus cetuximab plus XELOX as first-line treatment for patients with metastatic colorectal cancer (mCRC). ASCO Meeting. Abstracts, 2010, 28: 3540.
32. Adams RA, Meade AM, Seymour MT et al. Intermittent vs. continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomized phase 3 MRC COIN trial. Lancet Oncol, 2011, 12(7): 642–653.
33. Maughan TS, Adams RA, Smith CG et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet, 2011, 377(9783): 2103–2114.
34. Maughan, Adams RA, Smith CG et al. Addition of cetuximab to oxaliplatin-based combination chemotherapy (CT) in patients with KRAS wildtype advanced colorectal cancer (ACRC): a randomised superiority trial (MRC COIN). Eur J Cancer, 2009, 7(3): 4 (abstr 6LBA).
35. Garufi C, Torsello A, Tumolo S et al. POCHER (preoperative chemotherapy for hepatic resection) with cetuximab (Cmab) plus CPT-11/5- fluorouracil (5-U)/leucovorin(FA)/oxaliplatin (L-OHP) (CPT-11-FFL) in unresectable colorectal liver metastases (CLM). J Clin Oncol, 2009, 27: suppl. abstr e15020. 2009 ASCO Annual Meeting.
36. Robert C et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol, 2005, 6: 491-500.
37. Segaert S et al. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors Ann. Oncol., 2005, 16: 1425-1433.
38. Segaert S et al. The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. J. Dtsch. Dermatol. Ges., 2005, 3: 599-606.
39. Schrag D et al. Cetuximab therapy and symptomatic hypomagnesemia. Natl. Cancer Inst., 2005, 97(16): 1221-1810.
40. Saltz LB et al. Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc. Am. Soc. Clin. Oncol., 2001, 20(2a): Abstract 7.
41. Gullick WJ, Hughes CM, Mellon K et al. Immunohistochemical detection of the epidermal growth factor receptor in paraffin-embedded human tissues. J Pathol, 1991, 164: 285– 289.
42. Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer, 2006, 6: 803–812.
43. Nicholson RI, Gee JM, Happer ME et al. EGFR and cancer prognosis. Eur J Cancer, 2001, 37(Suppl. 4): S9–15.
44. Perez-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol, 2005, 23: 5235–5246.
Review
For citations:
Darenskaya AD, Dobrova NV, Medvedeva BM. Cetuximab in treatment of metastatic colorectal cancer: background and clinical observation. Meditsinskiy sovet = Medical Council. 2018;(19):32-41. (In Russ.) https://doi.org/10.21518/2079-701X-2018-19-32-41