Dabrafenib and its potential for the treatment of metastatic melanoma

Drug Design, Development and Therapy

Volumn 6, Issue , 2012, Pages 391-405

  Menzies, Alexander M ^a   Long, Georgina V ^a,b   Murali, Rajmohan ^c  

^a MELANOMA INSTITUTE AUSTRALIA   (Australia)

^b WESTMEAD HOSPITAL   (Australia)

^c MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

BRAF inhibitor; BRAF mutation; Clinical trial; GSK1120212; GSK2118436; Vemurafenib

Indexed keywords

B RAF KINASE; DABRAFENIB; DACARBAZINE; GLUTAMIC ACID; LYSINE; MITOGEN ACTIVATED PROTEIN KINASE; MUTANT PROTEIN; TRAMETINIB; VALINE; VEMURAFENIB;

BRAIN METASTASIS; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CANCER SURVIVAL; DISEASE SEVERITY; DRUG EFFICACY; DRUG FEVER; DRUG MECHANISM; ENZYME ACTIVITY; GENOTYPE; HUMAN; METASTATIC MELANOMA; MONOTHERAPY; MUTATION; PROGRESSION FREE SURVIVAL; REVIEW; SIGNAL TRANSDUCTION; SKIN CARCINOMA; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DISEASE-FREE SURVIVAL; DRUG DESIGN; HUMANS; IMIDAZOLES; INDOLES; MELANOMA; NEOPLASM METASTASIS; OXIMES; PROTO-ONCOGENE PROTEINS B-RAF; SKIN NEOPLASMS; SULFONAMIDES;

EID: 84872361487     PISSN: 11778881     EISSN: None     Source Type: Journal    
DOI: 10.2147/DDDT.S38998     Document Type: Review

References (122)

1. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36): 6199-6206.
2. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-954.
3. 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(9839):358-365.
4. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363(9):809-819.
5. Neagu M, Constantin C, Tanase C. Immune-related biomarkers for diagnosis/prognosis and therapy monitoring of cutaneous melanoma. Expert Rev Mol Diagn. 2010;10(7):897-919.
6. Hauschild A, Agarwala SS, Trefzer U, et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009;27(17): 2823-2830.
7. Flaherty KT, Lee SJ, Schuchter LM, et al. Final results of E2603: a double-blind, randomized phase III trial comparing carboplatin (C)/ paclitaxel (P) with or without sorafenib (S) in metastatic melanoma [abstract]. J Clin Oncol. 2010;28(15 Suppl): Abstract 8511.
8. 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(1): 158-166.
9. Eggermont AM, Schadendorf D. Melanoma and immunotherapy. Hematol Oncol Clin North Am. 2009;23(3):547-564 ix-x.
10. Patel PM, Suciu S, Mortier L, et al; EORTC Melanoma Group. Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV melanoma: final results of a randomised phase III study (EORTC 18032). Eur J Cancer. 2011;47(10):1476-1483.
11. Avril MF, Aamdal S, Grob JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004;22(6):1118-1125.
12. Atkins MB, Lotze MT, Dutcher J P, et al. High-dose recombinant inter- leukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7): 2105-2116.
13. Brose MS, Volpe P, Feldman M, et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res. 2002;62(23):6997-7000.
14. Wellbrock C, Ogilvie L, Hedley D, et al. V599EB-RAF is an oncogene in melanocytes. Cancer Res. 2004;64(7):2338-2342.
15. Wu J, Rosenbaum E, Begum S, Westra WH. Distribution of BRAF T1799A(V600E) mutations across various types of benign nevi: implications for melanocytic tumorigenesis. Am J Dermatopathol. 2007;29(6):534-537.
16. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135-2147.
17. Hacker E, Hayward NK, Dumenil T, James MR, Whiteman DC. The association between MC1R genotype and BRAF mutation status in cutaneous melanoma: findings from an Australian population. J Invest Dermatol. 2009;130(1):241-248.
18. Houben R, Becker JC, Kappel A, et al. Constitutive activation of the RAS-RAF signaling pathway in metastatic melanoma is associated with poor prognosis. J Carcinog. 2004;3(1):6.
19. Liu W, Kelly J W, Trivett M, et al. Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma. J Invest Dermatol. 2006;127(4):900-905.
20. Viros A, Fridlyand J, Bauer J, et al. Improving melanoma classifcation by integrating genetic and morphologic features. PLoS Med. 2008; 5(6):e120.
21. Thomas NE, Edmiston SN, Alexander A, et al. Number of nevi and early- life ambient UV exposure are associated with BRAF-mutant melanoma. Cancer Epidemiol Biomarkers Prev. 2007;16(5):991-997.
22. Long G V, Menzies AM, Nagrial AM, et al. Prognostic and clinico- pathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29(10):1239-1246.
23. Jakob JA, Bassett RL Jr, Ng CS, et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer. 2012; 118(16):4014-4023.
24. Edlundh-Rose E, Egyházi S, Omholt K, et al. NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res. 2006;16(6):471-478.
25. Omholt K, Platz A, Kanter L, Ringborg U, Hansson J. NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin Cancer Res. 2003;9(17):6483-6488.
26. Vredeveld LC, Possik PA, Smit MA, et al. Abrogation of BRAFV600E- induced senescence by PI3K pathway activation contributes to melanomagenesis. Genes Dev. 2012;26(10):1055-1069.
27. Dhomen N, Reis-Filho JS, da Rocha Dias S, et al. Oncogenic BRAF induces melanocyte senescence and melanoma in mice. Cancer Cell. 2009;15(4):294-303.
28. Zhuang D, Mannava S, Grachtchouk V, et al. C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells. Oncogene. 2008;27(52):6623-6634.
29. Hodis E, Watson IR, Kryukov G V, et al. A landscape of driver muta- tions in melanoma. Cell. 2012;150(2):251-263.
30. Moreau S, Saiag P, Aegerter P, et al. Prognostic value of BRAF (V600) mutations in melanoma patients after resection of metastatic lymph nodes. Ann Surg Oncol. Epub July 7, 2012.
31. Brissy S, Gaudy-Marqueste C, Mallet S, et al. BRAF mutation as a pejorative marker in metastatic melanoma [abstract]. J Clin Oncol. 2012;30(15 Suppl):Abstract 8555.
32. Rutkowski P, Jurkowska M, Gos A, et al. Correlations of molecular alterations in clinical stage III cutaneous melanoma with clinical- pathological features and patients outcome [abstract]. J Clin Oncol. 2012;30(15 Suppl): Abstract 8548.
33. Si L, Kong Y, Xu X, et al. Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort. Eur J Cancer. 2012;48(1):94-100.
34. Menzies AM, Haydu LE, Visintin L, et al. Distinguishing clinico- pathologic features of patients with V600E and V600K BRAF-mutant metastatic melanoma. Clin Cancer Res. 2012;18(12):3242-3249.
35. Arkenau HT, Kefford R, Long G V. Targeting BRAF for patients with melanoma. Br J Cancer. 2011;104(3):392-398.
36. Ugurel S, Thirumaran RK, Bloethner S, et al. B-RAF and N-RAS mutations are preserved during short time in vitro propagation and differentially impact prognosis. PLoS One. 2007;2(2):e236.
37. Cheng S, Chu P, Hinshaw M, Smith K, Maize J, Sferruzza A. Frequency of mutations associated with targeted therapy in malignant melanoma patients [abstract]. J Clin Oncol. 2011;29(15 Suppl):S549 Abstract 8597.
38. Amanuel B, Grieu F, Kular J, Millward M, Iacopetta B. Incidence of BRAF p.Val600Glu and p.Val600Lys mutations in a consecutive series of 183 metastatic melanoma patients from a high incidence region. Pathology. 2012;44(4):357-359.
39. Bauer J, Büttner P, Murali R, et al. BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site. Pigment Cell Melanoma Res. 2011;24(2):345-351.
40. Maldonado JL, Fridlyand J, Patel H, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. 2003;95(24): 1878-1890.
41. Rimoldi D, Salvi S, Liénard D, et al. Lack of BRAF mutations in uveal melanoma. Cancer Res. 2003;63(18):5712-5715.
42. Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457(7229):599-602.
43. Van Raamsdonk CD, Griewank KG, Crosby MB, et al. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010;363(23):2191-2199.
44. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009;9(1):28-39.
45. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64(19):7099-7109.
46. Eisen T, Ahmad T, Flaherty KT, et al. Sorafenib in advanced melanoma: a phase II randomised discontinuation trial analysis. Br J Cancer. 2006;95(5):581-586.
47. Flaherty KT, Redlinger M, Schuchter LM, Lathia CD, Weber BL, O'Dwyer PJ. Phase I/II, pharmacokinetic and pharmacodynamic trial of BAY 43-9006 alone in patients with metastatic melanoma [abstract]. J Clin Oncol. 2005;23(16 Suppl): Abstract 3037.
48. Flaherty KT, Schiller J, Schuchter LM, et al. A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. Clin Cancer Res. 2008;14(15):4836-4842.
49. Ott PA, Hamilton A, Min C, et al. A phase II trial of sorafenib in metastatic melanoma with tissue correlates. PLoS One. 2010;5(12):e15588.
50. Stuart DD, Aardalen KM, Lorenzana EG, et al. Characterization of a novel RAF kinase inhibitor that causes target dependent tumor regres- sion in human melanoma xenografts expressing mutant B-RAF [abstract 4856]. Proceedings of the 97th Annual Meeting of the American Association for Cancer Research; April 5, 2006; Washington, DC. Philadelphia, PA: American Association for Cancer Research; 2006.
51. Su Y, Vilgelm AE, Kelley MC, et al. RAF265 inhibits the growth of advanced human melanoma tumors. Clin Cancer Res. 2012;18(8): 2184-2198.
52. Sharfman WH, Hodi FS, Lawrence D P, et al. Results from the first- in-human (FIH) phase I study of the oral RAF inhibitor RAF265 administered daily to patients with advanced cutaneous melanoma [abstract]. J Clin Oncol. 2011;29(15 Suppl):Abstract 8508.
53. Bollag G, Hirth P, Tsai J, et al. Clinical effcacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010;467(7315):596-599.
54. Falchook GS, Long G V, Kurzrock R, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet. 2012;379(9829):1893-1901.
55. Anforth R, Fernandez-Penas P, Long G V. Cutaneous toxicities of RAF inhibitors. Lancet Oncol. In press 2012.
56. Halait H, Demartin K, Shah S, et al. Analytical performance of a real-time PCR-based assay for V600 mutations in the BRAF gene, used as the companion diagnostic test for the novel BRAF inhibi- tor vemurafenib in metastatic melanoma. Diagn Mol Pathol. 2012; 21(1):1-8.
57. Anderson S, Bloom KJ, Vallera DU, et al. Multisite analytic performance studies of a real-time polymerase chain reaction assay for the detection of BRAF V600E mutations in formalin-fxed, paraffin- embedded tissue specimens of malignant melanoma. Arch Pathol Lab Med. 2012;136(11):1385-1391.
58. Qu KZ, Pan Q, Zhang X, et al. Detection of BRAF mutations in melanoma: rate of mutation detection at codon 600 using Sanger sequencing as compared to the cobas 4800 method [abstract]. J Clin Oncol. 2012;30(15 Suppl):Abstract 8596.
59. Martin-Algarra S, Labiano T, Echeveste JI, et al. Use of cobas 4800 BRAF mutation test for the analysis of BRAF V600 mutations in cytological samples (CS) from metastatic melanoma (MM) [abstract]. J Clin Oncol. 2012;30(15 Suppl):Abstract 8572.
60. Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600- mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707-714.
61. Chapman PB, Hauschild A, Robert C, et al; BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-2516.
62. 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 [abstract]. J Clin Oncol. 2012; 30(15 Suppl):Abstract 8502.
63. 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(2):228-247.
64. Dummer R, Goldinger SM, Turtschi C P, et al. Open-label pilot study of vemurafenib in previously treated metastatic melanoma (mM) patients (pts) with symptomatic brain metastases (BM) [abstract]. Ann Oncol. 2012;23:ix366, Abstract 1125P.
65. Laquerre S, Arnone M, Moss K, et al. A selective RAF kinase inhibi- tor induces cell death and tumor regression of human cancer cell lines encoding B-RAFV600E mutation [abstract]. Mol Cancer Ther. 2009;8(12 Suppl 1):Abstract B88.
66. Kefford R, Arkenau H, Brown M P, 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 [abstract]. J Clin Oncol. 2010:28(15 Suppl):S611 Abstract 8503.
67. Kefford R, Arkenau HT, Brown M, et al. Selective inhibition of oncogenic BRAF V600E/K/D by GSK2118436: evidence of clinical activity in subjects with metastatic melanoma [abstract]. Pigment Cell Melanoma Res. 2010;23(6):912 Abstract 929.
68. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evalu- ate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205-216.
69. Trefzer U, Minor DR, Ribas A, et al. BREAK-2: a phase IIA trial of the selective BRAF kinase inhibitor GSK2118436 in patients with BRAF (V600E/K)-positive metastatic melanoma [abstract]. Pigment Cell Melanoma Res. 2011;24:1020 Abstract LBA1021-1021.
70. Long G V, Trefzer U, Davies MA, et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 study. Lancet Oncol. 2012;13(11):1087-1095.
71. Gounder MM, Spriggs DR. Inclusion of patients with brain metastases in phase I trials: an unmet need. Clin Cancer Res. 2011;17(12): 3855-3857.
72. Raizer JJ, Hwu WJ, Panageas KS, et al. Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro Oncol. 2008;10(2):199-207.
73. Azer MWF, Menzies AM, Haydu L, Kefford R, Long G V. Patterns of progression in patients (pts) with V600 BRAF-mutated melanoma metastatic to the brain treated with dabrafenib (GSK2118436) [abstract]. J Clin Oncol. 2012;30(15 Suppl):Abstract 8558.
74. Agarwala SS, Kirkwood JM, Gore M, et al. Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. J Clin Oncol. 2004;22(11):2101-2107.
75. Davies MA, Liu P, McIntyre S, et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer. 2011;117(8):1687-1696.
76. Carlino MS, Fogarty GB, Long G V. Treatment of melanoma brain metastases: a new paradigm. Cancer J. 2012;18(2):208-212.
77. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature. 2010;464(7287):427-430.
78. Heidorn SJ, Milagre C, Whittaker S, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell. 2010;140(2):209-221.
79. Hatzivassiliou G, Song K, Yen I, et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature. 2010;464(7287):431-435.
80. Lacouture ME, Chapman PB, Ribas A, et al. Presence of frequent under- lying RAS mutations in cutaneous squamous cell carcinomas and kera- toacanthomas (cuSCC/KA) that develop in patients during vemurafenib therapy [abstract]. J Clin Oncol. 2011;29(15 Suppl):Abstract 8520.
81. Anforth R, Tembe V, Blumetti T, Fernandez-Penas P. Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors. Pigment Cell Melanoma Res. 2012;25(5):569-572.
82. 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(3):207-215.
83. Oberholzer PA, Kee D, Dziunycz P, et al. RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors. J Clin Oncol. 2012;30(3):316-321.
84. Carlino MS, Saunders CA, Haydu LE, et al. (18)F-labelled fuorodeox- yglucose-positron emission tomography (FDG-PET) heterogeneity of response is prognostic in dabrafenib treated BRAF mutant metastatic melanoma. Eur J Cancer. Epub September 13, 2012.
85. McArthur GA, Puzanov I, Amaravadi R, et al. Marked, homogeneous, and early [18F]fuorodeoxyglucose-positron emission tomography responses to vemurafenib in BRAF-mutant advanced melanoma. J Clin Oncol. 2012;30(14):1628-1634.
86. Wilmott JS, Tembe V, Howle JR, et al. Intratumoral molecular het- erogeneity in a BRAF-mutant, BRAF inhibitor-resistant melanoma: a case illustrating the challenges for personalized medicine. Mol Cancer Ther. Epub September 7, 2012.
87. Rebecca V W, Smalley KS. Tumor heterogeneity and strategies to overcome kinase inhibitor resistance in cancer: lessons from melanoma. Expert Opin Investig Drugs. 2011;20(2):137-140.
88. Wilmott JS, Long G V, Howle JR, et al. Selective BRAF inhibitors induce marked T-cell infltration into human metastatic melanoma. Clin Cancer Res. 2012;18(5):1386-1394.
89. Sosman JA, Pavlick AC, Schuchter LM, et al. Analysis of molecular mecha- nisms of response and resistance to vemurafenib (vem) in BRAFV600E melanoma [abstract]. J Clin Oncol. 2012;30(15 Suppl):Abstract 8503
90. 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) [abstract]. J Clin Oncol. 2011; 29(15 Suppl):Abstract 8502.
91. Nathanson KL, Martin A, Letrero R, et al. Tumor genetic analy- ses of patients with metastatic melanoma treated with the BRAF inhibitor GSK2118436 (GSK436) [abstract]. J Clin Oncol. 2011; 29(15 Suppl): Abstract 8501.
92. Smalley KS, Lioni M, Dalla Palma M, et al. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E- mutated melanomas. Mol Cancer Ther. 2008;7(9):2876-2883.
93. Straussman R, Morikawa T, Shee K, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 2012;487(7408):500-504.
94. Shi H, Moriceau G, Kong X, et al. Melanoma whole-exome sequencing identifes (V600E)B-RAF amplifcation-mediated acquired B-RAF inhibitor resistance. Nature Commun. 2012;3:724.
95. Poulikakos PI, Persaud Y, Janakiraman M, et al. RAF inhibitor resis- tance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011;480(7377):387-390.
96. Villanueva J, Vultur A, Lee JT, et al. Acquired resistance to BRAF inhibi- tors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010;18(6):683-695.
97. Montagut C, Sharma S V, Shioda T, et al. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res. 2008;68(12):4853-4861.
98. 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(7326):973-977.
99. Wagle N, Emery C, Berger MF, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profling. J Clin Oncol. 2011;29(22):3085-3096.
100. Johannessen CM, Boehm JS, Kim S Y, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010;468(7326):968-972.
101. Gramza AW, Corless CL, Heinrich MC. Resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumors. Clin Cancer Res. 2009;15(24):7510-7518.
102. Nguyen KS, Kobayashi S, Costa DB. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer. 2009;10(4):281-289.
103. 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):782-789.
104. Kim KB, Lewis KD, 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]. Pigment Cell Melanoma Res. 2011;24:1021 Abstract LBA1021-1023.
105. Flaherty KT, Robert C, Hersey P, et al; METRIC Study Group. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107-114.
106. 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(18):1694-1703.
107. 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 [abstract]. Pigment Cell Melanoma Res. 2011;24:1022 Abstract LBA1021-1024.
108. Lee CI, Menzies AM, Haydu L, Clements A, Kefford R, Long G V. Correlates of fever in patients (pts) receiving combined dabrafenib (GSK2118436) plus trametinib (GSK1120212) for V600 BRAF- mutant metastatic melanoma (MM) [abstract]. J Clin Oncol. 2012; 30(15 Suppl):Abstract e19011.
109. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011; 364(26):2517-2526.
110. Hodi FS, O'Day SJ, McDermott D F, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723.
111. Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13(5):459-465.
112. Patnaik A, Kang S P, Tolcher AW, et al. Phase I study of MK-3475 (anti-PD-1 monoclonal antibody) in patients with advanced solid tumors [abstract]. J Clin Oncol. 2012;30(15 Suppl):Abstract 2512.
113. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454.
114. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti- PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455-2465.
115. Boni A, Cogdill A P, Dang P, et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lympho- cyte function. Cancer Res. 2010;70(13):5213-5219.
116. Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2010;102(7):493-501.
117. Petrella T, Verma S, Spithoff K, Quirt I, McCready D; Melanoma Disease Site Group. Adjuvant interferon therapy for patients at high risk for recurrent melanoma: an updated systematic review and practice guideline. Clin Oncol (R Coll Radiol). 2012;24(6):413-423.
118. Hoefich K P, Herter S, Tien J, et al. Antitumor effcacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E muta- tional status and sustained extracellular signal-regulated kinase/ mitogen-activated protein kinase pathway suppression. Cancer Res. 2009;69(7):3042-3051.
119. Torti VR, Wojciechowicz D, Hu W, et al. Epithelial tissue hyperplasia induced by the RAF inhibitor PF-04880594 is attenuated by a clinically well-tolerated dose of the MEK inhibitor PD-0325901. Mol Cancer Ther. 2012;11(10):2274-2283.
120. Schwartz GK, Robertson S, Shen A, et al. A phase I study of XL281, a selective oral RAF kinase inhibitor, in patients with advanced solid tumors [abstract]. J Clin Oncol. 2009;27(15 Suppl:Abstract 3513.
121. Ribas A, Flaherty KT. BRAF targeted therapy changes the treatment paradigm in melanoma. Nat Rev Clin Oncol. 2011;8(7):426-433.
122. Hauschild A, Grob JJ, Demidov LV, et al. Phase III, randomized, open-label, multicenter trial (BREAK-3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600E-mutated melanoma [abstract]. J Clin Oncol. 2012;30(15 Suppl):Abstract LBA8500.