nach oben

Erschienen in:

01.10.2014 | Original Research Article

FcγR and EGFR Polymorphisms as Predictive Markers of Cetuximab Efficacy in Metastatic Colorectal Cancer

verfasst von: Yuka Inoue, Shoichi Hazama, Shigeyoshi Iwamoto, Yasuhiro Miyake, Chu Matsuda, Ryouichi Tsunedomi, Naoko Okayama, Yuji Hinoda, Takahiro Yamasaki, Yutaka Suehiro, Shigefumi Yoshino, Junichi Sakamoto, Hideyuki Mishima, Masaaki Oka

Erschienen in: Molecular Diagnosis & Therapy | Ausgabe 5/2014

Einloggen, um Zugang zu erhalten

Abstract

Background and Objectives

Cetuximab shows activity in KRAS (Kirsten rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer (mCRC). Recent studies have demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in mCRC. We investigated the associations of FcγR (fragment C γ receptor) and EGFR (epidermal growth factor receptor) polymorphisms with the outcome of mCRC patients treated with cetuximab and FOLFIRI (folic acid/5-fluorouracil/irinotecan) as second-line therapy in the FLIER (Cetuximab Plus Folinic Acid/5-Fluorouracil/Irinotecan in KRAS Wild-Type Metastatic Colorectal Cancer as a Second-Line Treatment) study.

Methods

A total of 57 patients were evaluated in this study. The association of each polymorphism with the response rate, progression-free survival, and overall survival was analyzed.

Results

A tendency for longer overall survival was observed in patients with the EGFR CA repeat ≥36 genotype than in those with the ≤35 genotype (600 versus 483 days, P = 0.051). The haplotype containing the 131H and 158V alleles was associated with a lower response rate than the other haplotypes (P = 0.018). These results are contrary to previously published results.

Conclusion

Our data suggest that FcγR and EGFR CA repeat polymorphisms may be associated with the outcome of mCRC patients treated with cetuximab and FOLFIRI, although further investigations will be needed to confirm the association of FcγR and EGFR polymorphisms with the efficacy of cetuximab.

Nur mit Berechtigung zugänglich

Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220–41. doi:10.3322/caac.21149.PubMedCrossRef

Tsukuma H, Ajiki W, Ioka A, Oshima A. Survival of cancer patients diagnosed between 1993 and 1996: a collaborative study of population-based cancer registries in Japan. Jpn J Clin Oncol. 2006;36(9):602–7. doi:10.1093/jjco/hyl068.PubMedCrossRef

Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, 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):2103–14. doi:10.1016/s0140-6736(11)60613-2.PubMedCrossRefPubMedCentral

Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol. 2012;30(15):1755–62. doi:10.1200/jco.2011.38.0915.PubMedCrossRef

Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66(8):3992–5. doi:10.1158/0008-5472.can-06-0191.PubMedCrossRef

Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359(17):1757–65. doi:10.1056/NEJMoa0804385.PubMedCrossRef

Weiner GJ. Monoclonal antibody mechanisms of action in cancer. Immunol Res. 2007;39(1–3):271–8.PubMedCrossRef

van Sorge NM, van der Pol WL, van de Winkel JG. FcgammaR polymorphisms: implications for function, disease susceptibility and immunotherapy. Tissue Antigens. 2003;61(3):189–202.PubMedCrossRef

Parren PW, Warmerdam PA, Boeije LC, Arts J, Westerdaal NA, Vlug A, et al. On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2. J Clin Invest. 1992;90(4):1537–46. doi:10.1172/jci116022.PubMedCrossRefPubMedCentral

10.

Koene HR, Kleijer M, Algra J, Roos D, von dem Borne AE, de Haas M. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood. 1997;90(3):1109–14.PubMed

11.

Strome SE, Sausville EA, Mann D. A mechanistic perspective of monoclonal antibodies in cancer therapy beyond target-related effects. Oncologist. 2007;12(9):1084–95. doi:10.1634/theoncologist.12-9-1084.PubMedCrossRef

12.

Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003;21(21):3940–7. doi:10.1200/jco.2003.05.013.PubMedCrossRef

13.

Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol. 2008;26(11):1789–96. doi:10.1200/jco.2007.14.8957.PubMedCrossRef

14.

Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002;99(3):754–8.PubMedCrossRef

15.

Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Cancer. 2007;120(4):781–7. doi:10.1002/ijc.22370.PubMedCrossRef

16.

Kurai J, Chikumi H, Hashimoto K, Yamaguchi K, Yamasaki A, Sako T, et al. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res. 2007;13(5):1552–61. doi:10.1158/1078-0432.ccr-06-1726.PubMedCrossRef

17.

Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M, Blanchard F, et al. Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol. 2009;27(7):1122–9. doi:10.1200/jco.2008.18.0463.PubMedCrossRef

18.

Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, et al. FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol. 2007;25(24):3712–8. doi:10.1200/jco.2006.08.8021.PubMedCrossRef

19.

Pander J, Gelderblom H, Antonini NF, Tol J, van Krieken JH, van der Straaten T, et al. Correlation of FCGR3A and EGFR germline polymorphisms with the efficacy of cetuximab in KRAS wild-type metastatic colorectal cancer. Eur J Cancer. 2010;46(10):1829–34. doi:10.1016/j.ejca.2010.03.017.PubMedCrossRef

20.

Amador ML, Oppenheimer D, Perea S, Maitra A, Cusatis G, Iacobuzio-Donahue C, et al. An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors. Cancer Res. 2004;64(24):9139–43. doi:10.1158/0008-5472.can-04-1036.PubMedCrossRef

21.

Graziano F, Ruzzo A, Loupakis F, Canestrari E, Santini D, Catalano V, et al. Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer. J Clin Oncol. 2008;26(9):1427–34. doi:10.1200/jco.2007.12.4602.PubMedCrossRef

22.

Zhang W, Stoehlmacher J, Park DJ, Yang D, Borchard E, Gil J, et al. Gene polymorphisms of epidermal growth factor receptor and its downstream effector, interleukin-8, predict oxaliplatin efficacy in patients with advanced colorectal cancer. Clin Colorectal Cancer. 2005;5(2):124–31.PubMedCrossRef

23.

Goncalves A, Esteyries S, Taylor-Smedra B, Lagarde A, Ayadi M, Monges G, et al. A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment. BMC Cancer. 2008;8:169. doi:10.1186/1471-2407-8-169.PubMedCrossRefPubMedCentral

24.

Hsieh YY, Tzeng CH, Chen MH, Chen PM, Wang WS. Epidermal growth factor receptor R521K polymorphism shows favorable outcomes in KRAS wild-type colorectal cancer patients treated with cetuximab-based chemotherapy. Cancer Sci. 2012;103(4):791–6. doi:10.1111/j.1349-7006.2012.02225.x.PubMedCrossRef

25.

Iwamoto S, Hazama S, Kato T, Miyake Y, Fukunaga M, Matsuda C, et al. Multicenter phase II study of second-line cetuximab plus folinic acid/5-fluorouracil/irinotecan (FOLFIRI) in KRAS wild-type metastatic colorectal cancer: the FLIER study. Anticancer Res. 2014;34(4):1967–73.PubMed

26.

Okayama N, Nishioka M, Hazama S, Sakai K, Suehiro Y, Maekawa M, et al. The importance of evaluation of DNA amplificability in KRAS mutation testing with dideoxy sequencing using formalin-fixed and paraffin-embedded colorectal cancer tissues. Jpn J Clin Oncol. 2011;41(2):165–71. doi:10.1093/jjco/hyq173.PubMedCrossRef

27.

Maruta Y, Okayama N, Hiura M, Suehiro Y, Hirai H, Hinoda Y. Determination of ancestral allele for possible human cancer-associated polymorphisms. Cancer Genet Cytogenet. 2008;180(1):24–9. doi:10.1016/j.cancergencyto.2007.09.011.PubMedCrossRef

28.

Wang L, Hirayasu K, Ishizawa M, Kobayashi Y. Purification of genomic DNA from human whole blood by isopropanol-fractionation with concentrated Nal and SDS. Nucleic Acids Res. 1994;22(9):1774–5.PubMedCrossRefPubMedCentral

29.

Rodriguez J, Zarate R, Bandres E, Boni V, Hernandez A, Sola JJ, et al. Fc gamma receptor polymorphisms as predictive markers of cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer. Eur J Cancer. 2012;48(12):1774–80. doi:10.1016/j.ejca.2012.01.007.PubMedCrossRef

30.

Kono K, Takahashi A, Ichihara F, Sugai H, Fujii H, Matsumoto Y. Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer. Cancer Res. 2002;62(20):5813–7.PubMed

31.

Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A. CD4+ CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer. 2003;98(5):1089–99. doi:10.1002/cncr.11618.PubMedCrossRef

32.

Gebhardt F, Zanker KS, Brandt B. Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1. J Biol Chem. 1999;274(19):13176–80.PubMedCrossRef

33.

Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351(4):337–45. doi:10.1056/NEJMoa033025.PubMedCrossRef

Titel: FcγR and EGFR Polymorphisms as Predictive Markers of Cetuximab Efficacy in Metastatic Colorectal Cancer
verfasst von: Yuka Inoue
Shoichi Hazama
Shigeyoshi Iwamoto
Yasuhiro Miyake
Chu Matsuda
Ryouichi Tsunedomi
Naoko Okayama
Yuji Hinoda
Takahiro Yamasaki
Yutaka Suehiro
Shigefumi Yoshino
Junichi Sakamoto
Hideyuki Mishima
Masaaki Oka
Publikationsdatum: 01.10.2014
Verlag: Springer International Publishing
Erschienen in: Molecular Diagnosis & Therapy / Ausgabe 5/2014
Print ISSN: 1177-1062
Elektronische ISSN: 1179-2000
DOI: https://doi.org/10.1007/s40291-014-0103-6

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Background and Objectives

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2014

The Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES) −28C/G and −403G/A Polymorphisms and Asthma Risk: A Meta-analysis

Oncoapoptotic Markers in Oral Cancer: Prognostics and Therapeutic Perspective

Molecular Biomarkers in Interstitial Lung Diseases

Evaluation of a New High-Throughput Next-Generation Sequencing Method Based on a Custom AmpliSeq™ Library and Ion Torrent PGM™ Sequencing for the Rapid Detection of Genetic Variations in Long QT Syndrome

Blood-Based Biomarkers in Depression: Emerging Themes in Clinical Research