Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib in RAS-mutant relapsed or refractory myeloid malignancies

Cancer

Volumn 122, Issue 12, 2016, Pages 1871-1879

  Borthakur, Gautam ^a   Popplewell, Leslie ^b   Boyiadzis, Michael ^c   Foran, James ^d   Platzbecker, Uwe ^e   Vey, Norbert ^f   Walter, Roland B ^g   Olin, Rebecca ^h   Raza, Azra ⁱ   Giagounidis, Aristoteles ^j   Al Kali, Aref ^k   Jabbour, Elias ^a   Kadia, Tapan ^a   Garcia Manero, Guillermo ^a   Bauman, John W ^l   Wu, Yuehui ^m   Liu, Yuan ⁿ   Schramek, Dan ^o   Cox, Donna S ^p   Wissel, Paul ⁿ   Kantarjian, Hagop ^a   more..

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^c UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

^d UNIVERSITY OF ALABAMA HOSPITAL   (United States)

^e UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^f INSTITUT PAOLI CALMETTES   (France)

^g Fred Hutchinson Cancer Research Center   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ NewYork Presbyterian Hospital   (United States)

^j MARIEN HOSPITAL DÜSSELDORF   (Germany)

^k MAYO CLINIC   (United States)

^l IQVIA   (United States)

^m MERCK RESEARCH LABORATORIES   (United States)

ⁿ PFIZER INC   (United States)

^o GLAXOSMITHKLINE   (United States)

^p TEVA PHARMACEUTICALS   (Israel)

more..

Author keywords

acute myeloid leukemia; chronic myelomonocytic leukemia; KRAS; myelodysplastic syndromes; NRAS; trametinib

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; TRAMETINIB; KRAS PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; PROTEIN P21; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE;

ACUTE MYELOBLASTIC LEUKEMIA; ADULT; AGED; ANEMIA; ARTICLE; ATRIAL FIBRILLATION; BLURRED VISION; CEREBROVASCULAR ACCIDENT; CHRONIC MYELOMONOCYTIC LEUKEMIA; COHORT ANALYSIS; CONTINUOUS INFUSION; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEMALE; GENE MUTATION; HEART EJECTION FRACTION; HEART LEFT VENTRICLE FAILURE; HUMAN; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA; ONCOGENE K RAS; ONCOGENE N RAS; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QT PROLONGATION; RASH; SIDE EFFECT; STOMATITIS; THROMBOCYTOPENIA; VOMITING; BLOOD; CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFECTS; ENZYMOLOGY; GENETICS; KAPLAN MEIER METHOD; LEUKEMIA; LEUKEMIA, MYELOID, ACUTE; MIDDLE AGED; MUTATION; MYELODYSPLASTIC SYNDROMES; RECURRENT DISEASE; SIGNAL TRANSDUCTION; VERY ELDERLY; YOUNG ADULT;

ADULT; AGED; AGED, 80 AND OVER; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; KAPLAN-MEIER ESTIMATE; LEUKEMIA; LEUKEMIA, MYELOID, ACUTE; MAP KINASE SIGNALING SYSTEM; MIDDLE AGED; MUTATION; MYELODYSPLASTIC SYNDROMES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS P21(RAS); PYRIDONES; PYRIMIDINONES; RECURRENCE; YOUNG ADULT;

EID: 84961282550     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.29986     Document Type: Article

References (27)

1. Milella M, Kornblau SM, Estrov Z, et al., Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia. J Clin Invest. 2001; 108: 851-859.
2. Ricciardi MR, Mcqueen T, Chism D, et al., Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia. Leukemia. 2005; 19: 1543-1549.
3. Ricciardi MR, Scerpa MC, Bergamo P, et al., Therapeutic potential of MEK inhibition in acute myelogenous leukemia: rationale for "vertical" and "lateral" combination strategies. J Mol Med (Berl). 2012; 90: 1133-1144.
4. Navas TA, Mohindru M, Estes M, et al., Inhibition of overactivated P38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors. Blood. 2006; 108: 4170-4177.
5. Coghlan DW, Morley AA, Matthews JP, Bishop JF,. The incidence and prognostic significance of mutations in codon 13 of the N-Ras gene in acute myeloid leukemia. Leukemia. 1994; 8: 1682-1687.
6. Kohlmann A, Grossmann V, Klein HU, et al., Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol. 2010; 28: 3858-3865.
7. Padua RA, Carter G, Hughes D, et al., RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation. Leukemia. 1988; 2: 503-510.
8. Paschka P, Du J, Schlenk RF, et al., Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG). Blood. 2013; 121: 170-177.
9. Haferlach C, Dicker F, Kohlmann A, et al., AML with CBFB-MYH11 rearrangement demonstrate RAS pathway alterations in 92% of all cases including a high frequency of NF1 deletions. Leukemia. 2010; 24: 1065-1069.
10. Ricci C, Fermo E, Corti S, et al., RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant. Clin Cancer Res. 2010; 16: 2246-2256.
11. Itzykson R, Kosmider O, Renneville A, et al., Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol. 2013; 31: 2428-2436.
12. Spiekermann K, Bagrintseva K, Schwab R, Schmieja K, Hiddemann W,. Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells. Clin Cancer Res. 2003; 9: 2140-2150.
13. Gilliland DG, Griffin JD,. Role of FLT3 in leukemia. Curr Opin Hematol. 2002; 9: 274-281.
14. Chang JS, Santhanam R, Trotta R, et al., High levels of the BCR/ABL oncoprotein are required for the MAPK-hnRNP-E2 dependent suppression of C/EBPα-driven myeloid differentiation. Blood. 2007; 110: 994-1003.
15. Notari M, Neviani P, Santhanam R, et al., A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation. Blood. 2006; 107: 2507-2516.
16. Zhao Z, Chen CC, Rillahan CD, et al., Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis. Nat Genet. 2015; 47: 539-543.
17. Burgess MR, Hwang E, Firestone AJ, et al., Preclinical efficacy of MEK inhibition in Nras-mutant AML. Blood. 2014; 124: 3947-3955.
18. Cheson BD, Bennett JM, Kantarjian H, et al., Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000; 96: 3671-3674.
19. Infante JR, Fecher LA, Falchook GS, et al., Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol. 2012; 13: 773-781.
20. Falchook GS, Lewis KD, Infante JR, et al., Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial. Lancet Oncol. 2012; 13: 782-789.
21. Flaherty KT, Robert C, Hersey P, et al., Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012; 367: 107-114.
22. Kim KB, Kefford R, Pavlick AC, et al., Phase II study of the MEK1/MEK2 inhibitor trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol. 2013; 31: 482-589.
23. Cortes JE, Kantarjian H, Foran JM, et al., Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013; 31: 3681-3687.
24. Abdel-Wahab O, Adli M, Lafave LM, et al., ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell. 2012; 22: 180-193.
25. Pronier E, Almire C, Mokrani H, et al., Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors. Blood. 2011; 118: 2551-2555.
26. Sasaki M, Knobbe CB, Munger JC, et al., IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature. 2012; 488: 656-659.
27. Ravandi F, Alattar ML, Grunwald MR, et al., Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013; 121: 4655-4662.