Improved survival with MEK inhibition in BRAF-mutated melanoma

New England Journal of Medicine

Volumn 367, Issue 2, 2012, Pages 107-114

  Flaherty, Keith T ^a   Robert, Caroline ^b   Hersey, Peter ^d   Nathan, Paul ^e,f   Garbe, Claus ⁱ   Milhem, Mohammed ^q   Demidov, Lev V ^r   Hassel, Jessica C ^j   Rutkowski, Piotr ^s   Mohr, Peter ^k   Dummer, Reinhard ^t   Trefzer, Uwe ^l   Larkin, James M G ^g   Utikal, Jochen ^m,n,o   Dreno, Brigitte ^c   Nyakas, Marta ^u   Middleton, Mark R ^h   Becker, Jürgen C ^v   Casey, Michelle ^w   Sherman, Laurie J ^w   Wu, Frank S ^w   Ouellet, Daniele ^w   Martin, Anne Marie ^w   Patel, Kiran ^w   Schadendorf, Dirk ^p   more..

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c NANTES UNIVERSITY HOSPITAL   (France)

^d UNIVERSITY OF SYDNEY   (Australia)

^e MOUNT VERNON CANCER CENTRE   (United Kingdom)

^f INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^g ROYAL MARSDEN HOSPITAL   (United Kingdom)

^h CHURCHILL HOSPITAL   (United Kingdom)

ⁱ UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^j UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^k Elbekliniken Buxtehude   (Germany)

^l CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^m GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

ⁿ UNIVERSITY OF HEIDELBERG   (Germany)

^o UNIVERSITY OF HEIDELBERG   (Germany)

^p UNIVERSITY HOSPITAL ESSEN   (Germany)

^q UNIVERSITY OF IOWA HOSPITALS AND CLINICS   (United States)

^r N N BLOKHIN RUSSIAN CANCER RESEARCH CENTER   (Russian Federation)

^s INSTITUTE OF ONCOLOGY   (Poland)

^t UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^u OSLO UNIVERSITY HOSPITAL   (Norway)

^v Universitatsklinik fur Dermatologie und Venerologie   (Austria)

^w GLAXOSMITHKLINE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

DACARBAZINE; PACLITAXEL; TRAMETINIB;

ACNE; ADULT; ALOPECIA; ARTICLE; BRAF GENE; CANCER GROWTH; CANCER SURVIVAL; CHORIORETINOPATHY; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG WITHDRAWAL; EYE TOXICITY; FEMALE; GENE; GENE MUTATION; HEART EJECTION FRACTION; HEART LEFT VENTRICLE FAILURE; HUMAN; HYPERPROLIFERATIVE SKIN LESION; MAJOR CLINICAL STUDY; MALE; MELANOMA; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN BINDING; RETINA VEIN OCCLUSION; SIDE EFFECT; SKIN DEFECT; SQUAMOUS CELL CARCINOMA; SURVIVAL RATE; TREATMENT DURATION; TREATMENT RESPONSE; VOMITING;

EID: 84863673204     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1203421     Document Type: Article

References (23)

1. World cancer report 2008. Lyon, France: International Agency for Research on Cancer, 2008.
2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
3. Petrella T, Verma S, Spithoff K, et al. Adjuvant interferon therapy for patients at high risk for recurrent melanoma: an updated systematic review and practice guideline. Clin Oncol (R Coll Radiol) 2012 January 13 (Epub ahead of print).
4. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517-26.
5. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23. [Erratum, N Engl J Med 2010;363:1290.]
6. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507-16.
7. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54. (Pubitemid 34716871)
8. Jakob JA, Bassett RL Jr, Ng CS, et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer 2011 December 16 (Epub ahead of print).
9. Montagut C, Settleman J. Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Lett 2009;283:125-34.
10. Tsai J, Lee JT, Wang W, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A 2008;105: 3041-6. (Pubitemid 351723664)
11. Solit DB, Garraway LA, Pratilas CA, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006;439:358-62. (Pubitemid 43128863)
12. Gilmartin AG, Bleam MR, Groy A, et al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res 2011;17:989-1000.
13. Infante JR, Fecher LA, Nallapareddy S, et al. Safety and efficacy results from the first-in-human study of the oral MEK 1/2 inhibitor GSK1120212. Presented at the annual meeting of the American Society of Clinical Oncology, Chicago, June 4-8, 2010. abstract.
14. Kim KB, Lewis K, Pavlick A, et al. A Phase II study of the MEK1/MEK2 inhibitor GSK1120212 in metastatic BRAFV600E or K mutant cutaneous melanoma patients previously treated with or without a BRAF inhibitor. Pigment Cell Melanoma Res 2011;24:102. abstract.
15. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-55. (Pubitemid 13149996)
16. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
17. Kirkwood JM, Bastholt L, Robert C, et al. Phase II, open-label, randomized trial of the MEK 1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. Clin Cancer Res 2012;18:555-67.
18. Heidorn SJ, Milagre C, Whittaker S, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010;140:209-21.
19. Poulikakos PI, Zhang C, Bollag G, et al. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wildtype BRAF. Nature 2010;464:427-30.
20. Arnault JP, Mateus C, Escudier B, et al. Skin tumors induced by sorafenib; paradoxic RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. Clin Cancer Res 2012;18:263-72.
21. Su F, Viros A, Milagre C, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 2012;366:207-15.
22. Johannessen CM, Boehm JS, Kim SY, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 2010;468:968-72.
23. Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to BRAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 2010;468:973-7