Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): A randomised, open-label, phase 3 trial

The Lancet Oncology

Volumn 16, Issue 15, 2015, Pages 1493-1505

  Tournigand, Christophe ^a   Chibaudel, Benoist ^b   Samson, Benoit ^c   Scheithauer, Werner ^d   Vernerey, Dewi ^e   Mésange, Paul ^f   Lledo, Gérard ^g   Viret, Frédéric ^h   Ramée, Jean François ⁱ   Tubiana Mathieu, Nicole ^j   Dauba, Jérôme ^k   Dupuis, Olivier ^l   Rinaldi, Yves ^m   Mabro, May ⁿ   Aucoin, Nathalie ^o   Latreille, Jean ^c   Bonnetain, Franck ^e   Louvet, Christophe ^p   Larsen, Annette K ^f   André, Thierry ^q   de Gramont, Aimery ^b   more..

^a HENRI MONDOR HOSPITAL   (France)

^b Hopital Franco britannique   (France)

^c HÔPITAL CHARLES LEMOYNE   (Canada)

^d MEDICAL UNIVERSITY OF VIENNA   (Austria)

^e UNIVERSITY HOSPITAL OF BESANÇON   (France)

^f CENTRE DE RECHERCHE SAINT ANTOINE   (France)

^g Hopital Prive Jean Mermoz   (France)

^h INSTITUT PAOLI CALMETTES   (France)

ⁱ Center Catherine de Sienne   (France)

^j DUPUYTREN UNIVERSITY HOSPITAL   (France)

^k Centre Hospitalier Layne   (France)

^l Clinique Victor Hugo   (France)

^m HÔPITAL AMBROISE PARÉ   (France)

ⁿ FOCH HOSPITAL   (France)

^o Cite de la Sante de Laval   (Canada)

^p INSTITUT MUTUALISTE MONTSOURIS   (France)

^q ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BEVACIZUMAB; ERLOTINIB; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT;

ADULT; AGED; ALOPECIA; ANEMIA; ARTICLE; ASTHENIA; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER SURVIVAL; CONJUNCTIVITIS; CONTROLLED STUDY; DIARRHEA; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; EPISTAXIS; FEBRILE NEUTROPENIA; FEMALE; FOLLOW UP; HAND FOOT SYNDROME; HUMAN; HYPERTENSION; MAJOR CLINICAL STUDY; MALE; METASTATIC COLORECTAL CANCER; MUCOSA INFLAMMATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUROPATHY; NEUTROPENIA; OPEN STUDY; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL; RASH; THROMBOCYTOPENIA; THROMBOEMBOLISM; VOMITING; CLINICAL TRIAL; COLORECTAL NEOPLASMS; DISEASE FREE SURVIVAL; DRUG COMBINATION; MAINTENANCE CHEMOTHERAPY; MIDDLE AGED; SECONDARY;

AGED; ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; BEVACIZUMAB; COLORECTAL NEOPLASMS; DISEASE-FREE SURVIVAL; DRUG THERAPY, COMBINATION; ERLOTINIB HYDROCHLORIDE; FEMALE; HUMANS; MAINTENANCE CHEMOTHERAPY; MALE; MIDDLE AGED;

EID: 84954029886     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(15)00216-8     Document Type: Article

References (38)

1. de Gramont A Re-challenge and the concept of lines of therapy in metastatic colorectal cancer. Eur J Cancer 2011, 47(suppl 3):76-84.
2. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 2014, 15:1065-1075.
3. Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 2014, 371:1609-1618.
4. Venook A, Niedzwiecki D, Lenz H, 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). abstr LBA3.
5. Adams RA, Meade AM, Seymour MT, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol 2011, 12:642-653.
6. Chibaudel B, Maindrault-Goebel F, Lledo G, et al. Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol 2009, 27:5727-5733.
7. Tournigand C, Cervantes A, Figer A, et al. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer-a GERCOR study. J Clin Oncol 2006, 24:394-400.
8. Diaz-Rubio E, Gomez-Espana A, Massuti B, et al. First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist 2012, 17:15-25.
9. Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013, 369:1023-1034.
10. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009, 360:1408-1417.
11. Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009, 360:563-572.
12. Hecht JR, Mitchell E, Chidiac T, et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 2009, 27:672-680.
13. Townsley CA, Major P, Siu LL, et al. Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer. Br J Cancer 2006, 94:1136-1143.
14. Meyerhardt JA, Stuart K, Fuchs CS, et al. Phase II study of FOLFOX, bevacizumab and erlotinib as first-line therapy for patients with metastatic colorectal cancer. Ann Oncol 2007, 18:1185-1189.
15. Tournigand C, Lledo G, Delord J, et al. Modified Folfox7/bevacizumab or modified Xelox/bevacizumab with or without erlotinib in first-line metastatic colorectal cancer: Results of the feasibility phase of the DREAM-OPTIMOX3 study (GERCOR). Proc Am Soc Clin Oncol 2007, 25(suppl 18):4097.
16. Mésange P, Poindessous V, Savina A, et al. Bevacizumab exposure is accompanied by EGFR activation in colorectal cancer models providing a rationale for combinations of bevacizumab and erlotinib in the phase III DREAM study. Eur J Cancer 2013, 49(suppl 2):158.
17. Perez-Staub N, Chibaudel B, Figer A, et al. Who can benefit from chemotherapy holidays after first-line therapy for advanced colorectal cancer? A GERCOR study. J Clin Oncol 2008, 26:4037.
18. Tournigand C, Samson B, Scheithauer W, et al. Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal cancer (mCRC): efficacy and safety results of the International GERCOR DREAM phase III trial. Proc Am Soc Clin Oncol 2012, 30(suppl). abstr LBA3500.
19. Chibaudel B, Bonnetain F, Tournigand C, et al. Simplified prognostic model in patients with oxaliplatin-based or irinotecan-based first-line chemotherapy for metastatic colorectal cancer: a GERCOR study. Oncologist 2011, 16:1228-1238.
20. Tournigand C, Scheithauer W, Samson B, et al. Induction treatment in first-line with chemotherapy+bevacizumab (bev) in metastatic colorectal cancer: results from the gercor-DREAM phase III study. Proc Am Soc Clin Oncol 2013, 31(suppl 4). abstr 457.
21. Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013, 14:29-37.
22. Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. Proc Am Soc Clin Oncol 2012, 30:3499-3506.
23. Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 2014, 15:1236-1244.
24. Ciardiello F, Bianco R, Damiano V, et al. Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells. Clin Cancer Res 2000, 6:3739-3747.
25. Hirata A, Ogawa S, Kometani T, et al. ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res 2002, 62:2554-2560.
26. Larsen AK, Ouaret D, El Ouadrani K, et al. Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacol Ther 2011, 131:80-90.
27. Bianco R, Troiani T, Tortora G, et al. Intrinsic and acquired resistance to EGFR inhibitors in human cancer therapy. Endocr Relat Cancer 2005, 12(suppl 1):159-171.
28. Poindessous V, Ouaret D, El Ouadrani K, et al. EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory to combinations of monoclonal antibodies. Clin Cancer Res 2011, 17:6522-6530.
29. de Gramont A, Buyse M, Abrahantes JC, et al. Reintroduction of oxaliplatin is associated with improved survival in advanced colorectal cancer. J Clin Oncol 2007, 25:3224-3229.
30. Chibaudel B, Tournigand C, Bonnetain F, et al. Platinum-sensitivity in metastatic colorectal cancer: towards a definition. Eur J Cancer 2013, 49:3813-3820.
31. Hegewisch-Becker S, Graeven U, Lerchenmüller CA, et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 2015, 16:1355-1369.
32. Simkens LH, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 2015, 385:1843-1852.
33. Tebbutt NC, Wilson K, Gebski VJ, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group randomized phase III MAX study. J Clin Oncol 2010, 28:3191-3198.
34. Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013, 14:1077-1085.
35. Koeberle D, Betticher DC, von Moos R, et al. Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06). Ann Oncol 2015, 26:709-714.
36. Johnsson A, Hagman H, Frodin JE, et al. A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial. Ann Oncol 2013, 24:2335-2341.
37. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 2000, 355:1041-1047.
38. de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000, 18:2938-2947.