Skip to main content
main-content

Tipp

Weitere Artikel dieser Ausgabe durch Wischen aufrufen

Erschienen in: memo - Magazine of European Medical Oncology 2/2015

01.06.2015 | short review

New targets in metastatic colorectal cancer

verfasst von: MBA Priv.-Doz. Dr. Herbert Ulrich-Pur

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten
share
TEILEN

Abstract

At the moment, targeted therapy in metastatic colorectal cancer (mCRC) is a hot topic which is widely discussed in the scientific community. Approximately 25 % of all CRC patients present with metastases at the time of initial diagnosis, and an additional 50 % of them will develop metastases during the subsequent course of their disease, contributing to the high mortality rates reported. Novel targeted agents like monoclonal antibodies directed against vascular endothelial growth factors or against epidermal growth factor receptor combined with chemotherapy as well as multikinase inhibitors (in the salvage setting) have demonstrated to result in improved therapeutic outcome in patients with mCRC. Recent research efforts have focused to define patient subpopulations, who benefit most from the respective treatments. KRAS mutations in codons 12 and 13 are found in approximately 40 % of all patients with mCRC. These clinicopathologic characteristics generate consecutive activation of the mitogen-activated protein kinase pathway. Less frequent activating KRAS mutations occur in codons 61 and 146, and there are the NRAS mutations in codons 12, 13, and 61. The gene expression profiles of the RAS genes help to define those patients who are most likely to benefit from certain biological agents. This review discusses the therapeutic options based on recent publications.
Literatur
1.
Zurück zum Zitat Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403. PubMedCrossRef Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403. PubMedCrossRef
2.
Zurück zum Zitat Ferlay J, Parkin DM, Steliarova-Fouchera E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81. PubMedCrossRef Ferlay J, Parkin DM, Steliarova-Fouchera E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81. PubMedCrossRef
3.
Zurück zum Zitat Van Cutsem E, Cervantes A, Nordlinger B, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl. 3):iii1–9. PubMedCrossRef Van Cutsem E, Cervantes A, Nordlinger B, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl. 3):iii1–9. PubMedCrossRef
4.
Zurück zum Zitat Stintzing S. First-line treatment in mCRC: decisions based on molecular biomarkers. Oncol Res Treat. 2014;37(Suppl. 5):115(abstr V381). Stintzing S. First-line treatment in mCRC: decisions based on molecular biomarkers. Oncol Res Treat. 2014;37(Suppl. 5):115(abstr V381).
5.
Zurück zum Zitat Scheithauer W. Aktuelle Medikamentöse Therapie des kolorektalen Karzinoms. Pharmainformation. 2014;29(3):1. Scheithauer W. Aktuelle Medikamentöse Therapie des kolorektalen Karzinoms. Pharmainformation. 2014;29(3):1.
6.
Zurück zum Zitat Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486:532–6. PubMedCentralPubMed Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486:532–6. PubMedCentralPubMed
7.
Zurück zum Zitat Morris VK, San Lucas FA, Overman MJ, et al. Clinicopathologic characteristics and gene expression analyses of non-KRAS 12/13, RAS-mutated metastatic colorectal cancer. Ann Oncol. 2014;25:2008–14. PubMedCrossRef Morris VK, San Lucas FA, Overman MJ, et al. Clinicopathologic characteristics and gene expression analyses of non-KRAS 12/13, RAS-mutated metastatic colorectal cancer. Ann Oncol. 2014;25:2008–14. PubMedCrossRef
8.
Zurück zum Zitat 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):753–62. PubMedCrossRef 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):753–62. PubMedCrossRef
9.
Zurück zum Zitat Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25:1670–6. PubMedCrossRef Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25:1670–6. PubMedCrossRef
10.
Zurück zum Zitat Souglakos J, Androulakis N, Syrigos K, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer. 2006;94:798–805. PubMedCentralPubMedCrossRef Souglakos J, Androulakis N, Syrigos K, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer. 2006;94:798–805. PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Loupakis F, Cremolini C, Lonardi S, et al. Subgroup analyses in RAS mutant, BRAF mutant and all-wt mCRC pts treated with FOLFOXIRI plus bevacizumab (bev) or FOLFIRI plus bev in the TRIBE study. J Clin Oncol. 2014;32:abstr.3519. Loupakis F, Cremolini C, Lonardi S, et al. Subgroup analyses in RAS mutant, BRAF mutant and all-wt mCRC pts treated with FOLFOXIRI plus bevacizumab (bev) or FOLFIRI plus bev in the TRIBE study. J Clin Oncol. 2014;32:abstr.3519.
12.
Zurück zum Zitat Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab Plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–7. PubMedCrossRef Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab Plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32:2240–7. PubMedCrossRef
13.
Zurück zum Zitat Heinemann V, Fischer von Weikersthal L, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomized, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75. PubMedCrossRef Heinemann V, Fischer von Weikersthal L, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomized, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75. PubMedCrossRef
14.
Zurück zum Zitat Venook AP, Niedzwiecki D, Lenz HJ, et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). Proc Am Soc Clin Oncol. 2014;32(Suppl. 15):LBA3 (abstr). Venook AP, Niedzwiecki D, Lenz HJ, et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). Proc Am Soc Clin Oncol. 2014;32(Suppl. 15):LBA3 (abstr).
15.
Zurück zum Zitat Cremolini C, Loupakis F, Masi G, et al. FOLFOXIRI/bevacizumab versus FOLFIRI/bevacizumab as first-line treatment in unresectable metastatic colorectal cancer: results of phase III TRIBE trial by GONO Group. Ann Oncol. 2013;24(Suppl. 4):iv21. Cremolini C, Loupakis F, Masi G, et al. FOLFOXIRI/bevacizumab versus FOLFIRI/bevacizumab as first-line treatment in unresectable metastatic colorectal cancer: results of phase III TRIBE trial by GONO Group. Ann Oncol. 2013;24(Suppl. 4):iv21.
Metadaten
Titel
New targets in metastatic colorectal cancer
verfasst von
MBA Priv.-Doz. Dr. Herbert Ulrich-Pur
Publikationsdatum
01.06.2015
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 2/2015
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-014-0191-3