Trametinib (GSK1120212) in the treatment of melanoma

Expert Opinion on Pharmacotherapy

Volumn 14, Issue 5, 2013, Pages 619-627

  Salama, April K S ^a   Kim, Kevin B ^b  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS   (United States)

Author keywords

BRAF mutation; MAP kinase; MEK inhibitor; Metastatic melanoma; Trametinib

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; ARRY 438162; B RAF KINASE; DABRAFENIB; DACARBAZINE; K RAS PROTEIN; KI 67 ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PACLITAXEL; RAF PROTEIN; SELUMETINIB; TEMOZOLOMIDE; TRAMETINIB;

ARTHRALGIA; ARTICLE; BLURRED VISION; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER INHIBITION; CANCER SIZE; CANCER SURVIVAL; CENTRAL SEROUS RETINOPATHY; CHILL; COUGHING; CUTANEOUS MELANOMA; DIARRHEA; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY EYE; ENZYME PHOSPHORYLATION; FATIGUE; FEVER; GASTROINTESTINAL TOXICITY; HEADACHE; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; LOADING DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MELANOMA; MELANOMA CELL; METASTATIC MELANOMA; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; MUTATOR GENE; NAUSEA; NAUSEA AND VOMITING; OVERALL SURVIVAL; PERIORBITAL EDEMA; PERIPHERAL EDEMA; PROGRESSION FREE SURVIVAL; RASH; RECOMMENDED DRUG DOSE; RETINA VEIN OCCLUSION; SIDE EFFECT; SIGNAL TRANSDUCTION; SKIN CARCINOMA; SKIN DEFECT; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; UVEA MELANOMA; VISUAL IMPAIRMENT; VOMITING; WILD TYPE;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; MAP KINASE SIGNALING SYSTEM; MELANOMA; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MOLECULAR TARGETED THERAPY; PROTEIN KINASE INHIBITORS; PYRIDONES; PYRIMIDINONES; SKIN NEOPLASMS; TREATMENT OUTCOME;

EID: 84874993197     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2013.770475     Document Type: Article

References (55)

1. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000;18:158-66
2. Mouawad R, Sebert M, Michels J, et al. Treatment for metastatic malignant melanoma: old drugs and new strategies. Crit Rev Oncol Hematol 2010;74:27-39
3. Bedikian AY, Millward M, Pehamberger H, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 2006;24:4738-45
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. Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012;380:358-65
6. Hersh E, Del Vecchio M, Brown M, et al. Phase 3, randomized, open-label, multicenter trial of nab-paclitaxel (nab-P) vs dacarbazine (DTIC) in previously untreated patients with metastatic malignant melanoma (MMM). Pigment Cell Melanoma Res 2012;25:863
7. Rosenberg SA, Yang JC, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 1994;271:907-13
8. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999;17:2105-16
9. 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
10. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54
11. Hingorani SR, Jacobetz MA, Robertson GP, et al. Suppression of BRAF(V599E) in human melanoma abrogates transformation. Cancer Res 2003;63:5198-202
12. Ikenoue T, Hikiba Y, Kanai F, et al. Different effects of point mutations within the B-Raf glycine-rich loop in colorectal tumors on mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase and nuclear factor kappaB pathway and cellular transformation. Cancer Res 2004;64:3428-35
13. Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004;116:855-67
14. Chapman PB, Hauschild A, Robert C, et al. Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAFV600E-mutated melanoma. J Clin Oncol 2012;30(Suppl): abstract 8502
15. McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/ MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 2007;1773:1263-84
16. Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene 2007;26:3279-90
17. Pratilas CA, Solit DB. Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response. Clin Cancer Res 2010;16:3329-34
18. Solit DB, Garraway LA, Pratilas CA, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006;439:358-62
19. Crews CM, Alessandrini A, Erikson RL. The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science 1992;258:478-80
20. Yoon S, Seger R. The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors 2006;24:21-44
21. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005;353:2135-47
22. Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 2009;457:599-602
23. Rimoldi D, Salvi S, Lienard D, et al. Lack of BRAF mutations in uveal melanoma. Cancer Res 2003;63:5712-15
24. Van Raamsdonk CD, Griewank KG, Crosby MB, et al. Mutations in GNA11 in uveal melanoma. N Engl J Med 2010;363:2191-9
25. Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012;367:107-14
26. Kirkwood JM, Bastholt L, Robert C, et al. Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. Clin Cancer Res 2012;18:555-67
27. LoRusso PM, Krishnamurthi SS, Rinehart JJ, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers. Clin Cancer Res 2010;16:1924-37
28. Lorusso PM, Adjei AA, Varterasian M, et al. Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies. J Clin Oncol 2005;23:5281-93
29. Haura EB, Ricart AD, Larson TG, et al. A phase II study of PD-0325901, an oral MEK inhibitor, in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res 2010;16:2450-7
30. 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
31. Pratilas CA, Taylor BS, Ye Q, et al. (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci USA 2009;106:4519-24
32. Alessi DR, Cuenda A, Cohen P, et al. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem 1995;270:27489-94
33. Favata MF, Horiuchi KY, Manos EJ, et al. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem 1998;273:18623-32
34. 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;13:773-81
35. 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(8):782-9
36. Kim KB, Lewis K, Pavlick AC, et al. A Phase II study of the MEK1/ MEK2 inhibitor GSK1120212 in metastatic BRAF V600E or K mutant cutaneous melanoma patients previously treated with or without a BRAF inhibitor [abstract. LBA 1021-1023]. Pigment Cell Melanoma Res 2011;24(5):1021
37. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated braf in metastatic melanoma. N Engl J Med 2010;363:809-19
38. Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012;366:707-14
39. McArthur GA, Ribas A, Chapman PB, et al. Molecular analyses from a phase I trial of vemurafenib to study mechanism of action (MOA) and resistance in repeated biopsies from BRAF mutation-positive metastatic melanoma patients (pts). J Clin Oncol 2011;29(Suppl):abstract 8502
40. Nathanson KL, Martin A, Letrero R, et al. Tumor genetic analyses of patients with metastatic melanoma treated with the BRAF inhibitor GSK2118436 (GSK436). J Clin Oncol 2011;29(Suppl):abstract 8501
41. Sosman JA, Pavlick AC, Schuchter LM, et al. Analysis of molecular mechanisms of response and resistance to vemurafenib (vem) in BRAFV600E melanoma. J Clin Oncol 2012;30(Suppl): abstract 8503
42. Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to B-RAF (V600E) inhibition by RTK or N-RAS upregulation. Nature 2010;468:973-7
43. Emery CM, Vijayendran KG, Zipser MC, et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci USA 2009;106:20411-16
44. Poulikakos PI, Persaud Y, Janakiraman M, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 2011;480:387-90
45. Johannessen CM, Boehm JS, Kim SY, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 2010;468:968-72
46. Montagut C, Sharma SV, Shioda T, et al. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res 2008;68:4853-61
47. Infante JR, Falchook GS, Lawrence DP, et al. Phase I/II study to assess safety, pharmacokinetics, and efficacy of the oral MEK 1/2 inhibitor GSK1120212 (GSK212) dosed in combination with the oral BRAF inhibitor GSK2118436 (GSK436). J Clin Oncol 2011;29(Suppl):abstract CRA8503
48. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 2012;367:1694-703
49. Augsburger JJ, Correa ZM, Shaikh AH. Effectiveness of treatments for metastatic uveal melanoma. Am J Ophthalmol 2009;148:119-27
50. Kefford R, Arkenau H, Brown MP, et al. Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. J Clin Oncol 2010;28(15s Suppl): abstract 8503
51. Poulikakos PI, Zhang C, Bollag G, et al. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010;464:427-30
52. Rinehart J, Adjei AA, Lorusso PM, et al. Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J Clin Oncol 2004;22:4456-62
53. Dahlman KB, Xia J, Hutchinson K, et al. BRAFL597 mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov 2012;2:791-7
54. Flaherty K, Infante JR, Falchook GS, et al. Phase I/II expansion cohort of BRAF inhibitor GSK2118436 + MEK inhibitor GSK1120212 in patients with BRAF mutant metastatic melanoma who progressed on a prior BRAF inhibitor. Pigment Cell Melanoma Res 2011;24:1022
55. Ascierto PA, Berking C, Agarwala SS, et al. Efficacy and safety of oral MEK162 in patients with locally advanced and unresectable or metastatic cutaneous melanoma harboring BRAFV600 or NRAS mutations. J Clin Oncol 2012;30(Suppl):abstract 8511