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Erschienen in: Journal of Cancer Research and Clinical Oncology 3/2015

01.03.2015 | Original Article – Clinical Oncology

Inclusion of targeted therapies in the standard of care for metastatic colorectal cancer patients in a German cancer center: the more the better?!

verfasst von: Markus Moehler, Thomas Thomaidis, Chourouk Zeifri, Tareq Barhoom, Jens Marquardt, Philippe Ploch, Joern Schattenberg, Annett Maderer, Carl Christoph Schimanski, Arndt Weinmann, Marcus Alexander Woerns, Anne L. Kranich, Jens M. Warnecke, Peter Robert Galle

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2015

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Abstract

Purpose

Significant prolongation of overall survival (OS) has been reached in metastatic colorectal cancer (mCRC) treatment within the last 5–10 years. Our study was conducted in order to evaluate and compare OS of different standard of care treatment options in a university-based outpatient clinic.

Methods

One hundred and three mCRC patients were identified by retrospective analysis and treated according to available guidelines. OS was analyzed according to the different combinations of first- and second-line treatments.

Results

mCRC patients revealed an mOS of 34.4 months. Patients receiving anti-vascular endothelial growth factor (VEGF) blockade in at least one treatment line showed a significantly longer survival time (p = 0.0056) versus patients without any bevacizumab. No OS differences were detected comparing the different first- and second-line chemotherapy (CTX) strategies in the unselected population. However, wild-type (wt) Kras patients treated with anti-epidermal growth factor receptor (EGFR) therapy plus CTX in first-line therapy showed significantly longer OS compared to those receiving only additional VEGF inhibition or no targeted therapy (p = 0.0056; mOS 46.8 vs. 20.4 months, respectively). wt Kras patients profited in trend (p = 0.076) from CTX combinations of first-line anti-EGFR followed by second-line anti-VEGF compared to first-line anti-VEGF followed by second-line anti-EGFR (mOS 46.8 vs. 19.2 months, respectively).

Conclusions

Our results indicate successful allocation of the current mCRC treatment according to the Kras status. Differences in OS of wt Kras patients indicated the further need for randomized trials to define the potential benefit of sequential therapy with EGFR inhibition in first-line therapy followed by VEGFR inhibition vice versa.
Literatur
Zurück zum Zitat Awada A, Gil T, Whenham N, Van Hamme J, Besse-Hammer T, Brendel E et al (2011) Safety and pharmacokinetics of sorafenib combined with capecitabine in patients with advanced solid tumors: results of a phase 1 trial. J Clin Pharmacol 51:1674–1684. doi:10.1177/0091270010386226 CrossRefPubMed Awada A, Gil T, Whenham N, Van Hamme J, Besse-Hammer T, Brendel E et al (2011) Safety and pharmacokinetics of sorafenib combined with capecitabine in patients with advanced solid tumors: results of a phase 1 trial. J Clin Pharmacol 51:1674–1684. doi:10.​1177/​0091270010386226​ CrossRefPubMed
Zurück zum Zitat Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37. doi:10.1016/S1470-2045(12)70477-1 CrossRefPubMed Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37. doi:10.​1016/​S1470-2045(12)70477-1 CrossRefPubMed
Zurück zum Zitat Cutsem EV, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maurel J et al (2007) Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial. J Clin Oncol 25:4000 Cutsem EV, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maurel J et al (2007) Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial. J Clin Oncol 25:4000
Zurück zum Zitat Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M et al (2010) 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 28:4697–4705. doi:10.1200/JCO.2009.27.4860 CrossRefPubMed Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M et al (2010) 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 28:4697–4705. doi:10.​1200/​JCO.​2009.​27.​4860 CrossRefPubMed
Zurück zum Zitat Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C et al (2007) 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 25:1670–1676. doi:10.1200/JCO.2006.09.0928 CrossRefPubMed Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C et al (2007) 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 25:1670–1676. doi:10.​1200/​JCO.​2006.​09.​0928 CrossRefPubMed
Zurück zum Zitat Heinemann V, Weikersthal LFV, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran S-E et al. (2013) Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3). J Clin Oncol 31: LBA3506 Heinemann V, Weikersthal LFV, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran S-E et al. (2013) Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3). J Clin Oncol 31: LBA3506
Zurück zum Zitat Hurwitz HI, Fehrenbacher L, Hainsworth JD, Heim W, Berlin J, Holmgren E et al (2005) Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 23:3502–3508. doi:10.1200/JCO.2005.10.017 CrossRefPubMed Hurwitz HI, Fehrenbacher L, Hainsworth JD, Heim W, Berlin J, Holmgren E et al (2005) Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 23:3502–3508. doi:10.​1200/​JCO.​2005.​10.​017 CrossRefPubMed
Zurück zum Zitat International Agency for Research on Cancer (2010) GLOBOCAN 2008 v2.0, Estimated cancer incidence, mortality prevalence and disability-adjusted life years (DALYs) worldwide in 2008. http://globocan.iarc.fr/ International Agency for Research on Cancer (2010) GLOBOCAN 2008 v2.0, Estimated cancer incidence, mortality prevalence and disability-adjusted life years (DALYs) worldwide in 2008. http://​globocan.​iarc.​fr/​
Zurück zum Zitat Kindler HL, Friberg G, Skoog L, Wade-Oliver K, Vokes EE (2005) Phase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer. Am J Clin Oncol 28:340–344CrossRefPubMed Kindler HL, Friberg G, Skoog L, Wade-Oliver K, Vokes EE (2005) Phase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer. Am J Clin Oncol 28:340–344CrossRefPubMed
Zurück zum Zitat Lawrence YR, Golan T, Aderka D, Shani A, Zach L, Ben-David M et al (2012) Changing prognosis of metastatic colorectal adenocarcinoma (mCRC) 1988–2008 within the general population: has everyone benefitted? J Clin Oncol 30:e14143 Lawrence YR, Golan T, Aderka D, Shani A, Zach L, Ben-David M et al (2012) Changing prognosis of metastatic colorectal adenocarcinoma (mCRC) 1988–2008 within the general population: has everyone benefitted? J Clin Oncol 30:e14143
Zurück zum Zitat Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P 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. doi:10.1200/JCO.2006.06.7595 CrossRefPubMed Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P 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. doi:10.​1200/​JCO.​2006.​06.​7595 CrossRefPubMed
Zurück zum Zitat Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Trenta P et al (2013) FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (MCRC): results of the phase III randomized TRIBE trial. J Clin Oncol 31:336 Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Trenta P et al (2013) FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (MCRC): results of the phase III randomized TRIBE trial. J Clin Oncol 31:336
Zurück zum Zitat Moehler M, Mueller A, Trarbach T, Lordick F, Seufferlein T, Kubicka S et al (2010) Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol 22:1358–1366. doi:10.1093/annonc/mdq591 CrossRefPubMed Moehler M, Mueller A, Trarbach T, Lordick F, Seufferlein T, Kubicka S et al (2010) Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol 22:1358–1366. doi:10.​1093/​annonc/​mdq591 CrossRefPubMed
Zurück zum Zitat Oliner KS, Douillard J-Y, Siena S, Tabernero J, Burkes RL, Barugel ME et al. (2013) Analysis of KRAS/NRAS and BRAF mutations in the phase III PRIME study of panitumumab (pmab) plus FOLFOX versus FOLFOX as first-line treatment (tx) for metastatic colorectal cancer (mCRC). J Clin Oncol 31. Abstract 3511 Oliner KS, Douillard J-Y, Siena S, Tabernero J, Burkes RL, Barugel ME et al. (2013) Analysis of KRAS/NRAS and BRAF mutations in the phase III PRIME study of panitumumab (pmab) plus FOLFOX versus FOLFOX as first-line treatment (tx) for metastatic colorectal cancer (mCRC). J Clin Oncol 31. Abstract 3511
Zurück zum Zitat Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y et al (2010) 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 28:4706–4713. doi:10.1200/JCO.2009.27.6055 CrossRefPubMed Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y et al (2010) 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 28:4706–4713. doi:10.​1200/​JCO.​2009.​27.​6055 CrossRefPubMed
Zurück zum Zitat Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019. doi:10.1200/JCO.2007.14.9930 CrossRefPubMed Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019. doi:10.​1200/​JCO.​2007.​14.​9930 CrossRefPubMed
Zurück zum Zitat Samalin E, Bouche O, Thezenas S, Francois E, Adenis A, Bennouna J et al (2014) Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial. Br J Cancer 110:1148–1154. doi:10.1038/bjc.2013.813 CrossRefPubMed Samalin E, Bouche O, Thezenas S, Francois E, Adenis A, Bennouna J et al (2014) Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial. Br J Cancer 110:1148–1154. doi:10.​1038/​bjc.​2013.​813 CrossRefPubMed
Zurück zum Zitat Shike M, Winawer SJ, Greenwald PH, Bloch A, Hill MJ, Swaroop SV (1990) Primary prevention of colorectal cancer. The WHO collaborating centre for the prevention of colorectal cancer. Bull World Health Organ 68:377–385PubMedCentralPubMed Shike M, Winawer SJ, Greenwald PH, Bloch A, Hill MJ, Swaroop SV (1990) Primary prevention of colorectal cancer. The WHO collaborating centre for the prevention of colorectal cancer. Bull World Health Organ 68:377–385PubMedCentralPubMed
Zurück zum Zitat Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311–2319. doi:10.1200/JCO.2007.13.1193 CrossRefPubMed Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311–2319. doi:10.​1200/​JCO.​2007.​13.​1193 CrossRefPubMed
Zurück zum Zitat Stintzing S, Jung A, Rossius L, Modest DP, Fischer von Weikersthal L, Decker T et al. (2013) Analysis of KRAS/NRAS and BRAF mutations in FIRE-3: A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. European Cancer Congress 2013. Abstract 17 Stintzing S, Jung A, Rossius L, Modest DP, Fischer von Weikersthal L, Decker T et al. (2013) Analysis of KRAS/NRAS and BRAF mutations in FIRE-3: A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. European Cancer Congress 2013. Abstract 17
Zurück zum Zitat Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D 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. doi:10.1200/JCO.2004.05.113 CrossRefPubMed Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D 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. doi:10.​1200/​JCO.​2004.​05.​113 CrossRefPubMed
Zurück zum Zitat Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B 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. doi:10.1200/JCO.2006.08.1620 CrossRefPubMed Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B 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. doi:10.​1200/​JCO.​2006.​08.​1620 CrossRefPubMed
Zurück zum Zitat Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417. doi:10.1056/NEJMoa0805019 CrossRefPubMed Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417. doi:10.​1056/​NEJMoa0805019 CrossRefPubMed
Metadaten
Titel
Inclusion of targeted therapies in the standard of care for metastatic colorectal cancer patients in a German cancer center: the more the better?!
verfasst von
Markus Moehler
Thomas Thomaidis
Chourouk Zeifri
Tareq Barhoom
Jens Marquardt
Philippe Ploch
Joern Schattenberg
Annett Maderer
Carl Christoph Schimanski
Arndt Weinmann
Marcus Alexander Woerns
Anne L. Kranich
Jens M. Warnecke
Peter Robert Galle
Publikationsdatum
01.03.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1829-6

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