Vemurafenib for the treatment of melanoma

Expert Opinion on Pharmacotherapy

Volumn 13, Issue 17, 2012, Pages 2533-2543

  Jordan, Emmet John ^a   Kelly, Catherine M ^b  

^a WATERFORD REGIONAL HOSPITAL   (Ireland)

^b MATER MISERICORDIAE UNIVERSITY HOSPITAL   (Ireland)

Author keywords

Adverse effects; BRAF mutation; Melanoma; Safety; V600E mutation

Indexed keywords

4 DIALLYLAMINOMETHYLENE 1,3,4,7,10,11,12,13,14,15,16,17 DODECAHYDRO 6 HYDROXY 1 METHOXYMETHYL 10,13 DIMETHYL 3,7,17 TRIOXO 2 OXACYCLOPENTA[A]PHENANTHREN 11 YL ACETATE; B RAF KINASE; BEVACIZUMAB; BUPARLISIB; DABRAFENIB; DACARBAZINE; HEAT SHOCK PROTEIN 90 INHIBITOR; IPILIMUMAB; METFORMIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MYDRIATIC AGENT; RAF PROTEIN; RAS PROTEIN; SORAFENIB; STEROID; TRAMETINIB; UNCLASSIFIED DRUG; VEMURAFENIB; WARFARIN; XL 888;

ACTINIC KERATOSIS; ALOPECIA; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTHRALGIA; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CANCER RESISTANCE; CANCER SURVIVAL; CHEMOTHERAPY INDUCED EMESIS; DARIER DISEASE; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG ERUPTION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG POTENTIATION; DRUG SAFETY; DRUG STRUCTURE; DRY SKIN; ERYTHEMA NODOSUM; FATIGUE; GENE MUTATION; HAND FOOT SYNDROME; HUMAN; HYPERKERATOSIS; INOPERABLE CANCER; KERATOACANTHOMA; KERATOSIS; LIVER FUNCTION TEST; MACULOPAPULAR RASH; MAXIMUM PLASMA CONCENTRATION; MELANOMA; METASTATIC MELANOMA; MYALGIA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL; PHOTOSENSITIVITY; PROGRESSION FREE SURVIVAL; QT PROLONGATION; RECOMMENDED DRUG DOSE; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SKIN CARCINOGENESIS; SKIN CARCINOMA; SKIN TOXICITY; SQUAMOUS CELL CARCINOMA; STEVENS JOHNSON SYNDROME; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT RESPONSE; UVEITIS;

ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; INDOLES; MELANOMA; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; SULFONAMIDES;

EID: 84869751808     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2012.737780     Document Type: Review

References (76)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. A Cancer Journal for Clinicians 2012;62(1):10-29
2. Lens MB, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol 2004;150:179-85
3. Ives NJ, Stowe RL, Lorigan P, et al. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J Clin Oncol 2007;25:5426-34
4. Lee SM, Betticher DC, Thatcher N. Melanoma: Chemotherapy. Br Med Bull 1995;51:609-30
5. Stevens MFG, Hickman JA, Langdon SP, et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5- tetrazin-4(3H)-one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res 1987;47:5846-52
6. Baer JC, Freeman AA, Newlands ES, et al. Depletion of O6-alkylguanine. DNA alkyltransferase correlates with potentiation of temozolomide and CCNU cytotoxicity in human tumour cells. Br J Cancer 1993;67:1299-302
7. D'Atri S, Piccioni D, Castellano A, et al. Chemosensitivity to triazene compounds and O6-alkylguanine. DNA alkyltransferase levels: studies with blasts of leukaemic patients. Ann Oncol 1995;6:389-93
8. Tisdale MJ. Antitumour imidazotetrazines: XV. Role of guanine O6 alkylation in the mechanism of cytotoxicity of imidazotetrazinones. Biochem Pharmacol 1987;36:457-62
9. Bleehen NM, Newlands ES, Lee SM, et al. Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. J Clin Oncol 1995;13:910-13
10. 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
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;22:1118-25
12. Patel PM, Suciu S, Mortier L, et al. 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):1476-83
13. Eggermont AMM, Kirkwood JM. Re-evaluating the role of dacarbazine in metastatic melanoma: What have we learned in 30 years? Eur J Cancer 2004;40:1825-36
14. Melero I, Hervas-Stubbs S, Glennie M, et al. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer 2007;7:95-106
15. Garbe C, Eigentler TK, Keilholz U, et al. Systematic review of medical treatment in melanoma: current status and future prospects. Oncologist. 2011;16(1):5-24
16. O'Day SJ, Hamid O, Urba WJ. Targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4): a novel strategy for the treatment of melanoma and other malignancies. Cancer 2007;110:2614-27
17. Fong L, Small EJ. Anti-cytotoxic T lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment. J Clin Oncol 2008;26:5275-83
18. Robert C, Ghiringhelli F. What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? Oncologist 2009;14:848-61
19. 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
20. Weber J, Thompson JA, Hamid O, et al. A randomized, double-blind, placebocontrolled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res 2009;15:5591-8
21. Wolchok JD, Neyns B, Linette G, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 2010;11:155-64
22. Day SJ, Maio M, Chiarion-Sileni V, et al. Efficacy and safety of ipilimumab monotherapy in patients with previously treated, advanced melanoma: a multicenter, single-arm phase II study. Ann Oncol 2010;21(8):1712-17
23. 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
24. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517-26
25. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54
26. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005;353:2135-47
27. Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol 2011;29:1239-46
28. Thomas RK, Baker AC, Debiasi RM, et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet 2007;39(3):347-51
29. Garnett MJ, Marais R. Guilty as charged: B-raf is a human oncogene. Cancer Cell 2004;6:313-19
30. Hacker E, Hayward NK, Dumenil T, et al. The association between MC1R genotype and BRAF mutation status in cutaneous melanoma: findings from an Australian population. J Invest Dermatol 2010;130:241-8
31. Liu W, Kelly JW, Trivett M, et al. Distinct clinical and pathological features are associated with the BRAF(T1799A (V600E)) mutation in primary melanoma. J Invest Dermatol 2006;127:900-5
32. Viros A, Fridlyand J, Bauer J, et al. Improving melanoma classification by integrating genetic and morphologic features. PLoS Med 2008;5:e120
33. 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;16:991-7
34. 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 USA 2008;105:3041-6
35. Sondergaard JN, Nazarian R, Wang Q, et al. Differential sensitivity of melanoma cell lines with BRAF V600E mutation to the specific Raf inhibitor PLX4032. J Transl Med 2010;8:39
36. Bollag G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010;467:596-9
37. Sala E, Mologni L, Truffa S, et al. BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol Cancer Res 2008;6:751-9
38. Hatzivassiliou G, Song K, Yen I, et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 2010;464:431-5
39. 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):207-15
40. 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
41. Infante JR, Falchook GS, Lawrence DP, et al. Phase I/II study to assess safety, pharmacokinetics, and efficacy of the oral MEK1/2 inhibitor GSK1120212 (GSK212) dosed in combination with the oral BRAF inhibitor GSK2118436 (GSK436) (abstract). J Clin Oncol 2011;29:Suppl . Outlines evaluation of MEK and BRAF inhibitors. Available from: www.ema.europa.eu/docs
42. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010;363:809-19
43. Ribas A, Kim KB, Schuchter LM, et al. BRIM-2: an open-label, multicenter phase II study of vemurafenib in previously treated patients with BRAFV600E mutation positive Melanoma. abstract. J Clin Oncol 2011;29(Suppl):8509
44. 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
45. Chapman PB, Hauschild A, Robert C, et al. For the BRIM-3 Study Group: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507-16
46. 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):abstr 8502
47. 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):358-65
48. Boyd KP, Vincent B, Andea A, et al. Nonmalignant cutaneous findings associated with vemurafenib use in patients with metastatic melanoma. J Am Acad Dermatol 2012; Epub ahead of print 51. Wang CM, Fleming KF, Hsu S. A case of vemurafenib-induced keratosis pilaris-like eruption. Dermatol Online J 2012;18(4):7
49. Dummer R, Rinderknecht J, Goldinger SM. Ultraviolet A and photosensitivity during vemurafenib therapy. N Engl J Med 2012;366(5):480-1
50. Williams VL, Cohen PR, Stewart DJ. Sorafenib-induced premalignant and malignant skin lesions. Int J Dermatol 2011;50:396-402
51. Kwon EJ, Kish LS, Jaworsky C. The histologic spectrum of epithelial neoplasms induced by sorafenib. J Am Acad Dermatol 2009;61:522-7
52. 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
53. 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):316-21
54. Huang V, Hepper D, Anadkat M, et al. Cutaneous toxic effects associated with vemurafenib and inhibition of the BRAF pathway. Arch Dermatol 2012;148(5):628-33
55. Zimmer L, Hillen U, Livingstone E, et al. Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition. J Clin Oncol 2012;30(19):2375-83
56. Available from: www.drugguide.com/ddo/ub/view/Davis-Drug-Guide/109622/ all/vemurafenib 60. Walston S, Gordon N, Chakravarti A. Resistance to BRAF inhibition in melanoma: An epigenetic approach. J Clin Oncol 2012;30(Suppl):abstr e19040
57. 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
58. Johannessen CM, Boehm JS, Kim SY, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 2010;468:968-72
59. Solit DB, Rosen N. Resistance to BRAF inhibition in melanomas. N Engl J Med 2011;364(8):772-4
60. Shi H, Moriceau G, Kong X, et al. Melanoma whole-exome sequencing identifies (V600E)BRAF amplification-mediated acquired BRAF inhibitor resistance. Nature Commun 2012;3:724
61. 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
62. Hersey P. Targeting histone deacetylase to overcome resistance of B-RAFV600E melanoma cells to apoptosis. J Clin Oncol 2011;29(Suppl):abstr 8516
63. Flaherty K, Infante JR, Falchook GS, et al. Phase I/II study of BRA Fi GSK2118436 + ME Ki GSK1120212 in patients with BRAF mutant metastatic melanoma who progressed on a prior BRAFi. Pigment Cell Melanoma Res 2011;25(1):E1-E11
64. 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 2001;29:Abstr CRA 8503
65. Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012;367(2):107-14
66. Weber JS, Flaherty KT, Infante JR, et al. Updated safety and efficacy results from a Phase I/II study of the oral BRAF inhibitor dabrafenib (GSK2118436) combined with the oral MEK 1/2 inhibitor trametinib (GSK1120212) in patients with BRAFi-naive metastatic melanoma. J Clin Oncol 2012;30(Suppl); abstract 8510
67. Ph I/II Ipilimumab Vemurafenib Combo. Clinicaltrials.gov. Available from: http://clinicaltrials.gov/ct2/show/NCT01400451? term=vemurafenib&rank=5
68. Ascierto PA, Simeone E, Giannarelli D, et al. Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J Transl Med 2012;10:107
69. Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004;22:2865-72
70. de la Monte SM, Moore GW, Hutchins GM. Patterned distribution of metastases from malignant melanoma in humans. Cancer Res 1983;43:3427-33
71. Falchook GS, Long GV, Kurzrock R. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet. 2012;379(9829):1893-901
72. Kirkwood JM, Long GV, Trefzer U, et al. BREAK-MB: A phase II study assessing overall intracranial response rate to dabrafenib (GSK2118436) in patients with BRAF V600E/k mutation-positive melanoma with brain metastases. 2012 ASCO Annual Meeting. Abstract 8501 Presented June 4; 2012
73. Villanueva J, Vultur A, Lee JT, et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell 2010;18:683-95
74. Halaban R, Zhang W, Bacchiocchi A, et al. PLX4032, a selective BRAF (V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res 2010;23:190-200
75. Rubinstein JC, Sznol M, Pavlick AC, et al. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J Transl Med 2010;8:67
76. Trefzer U, Minor D, Ribas A, et al. BREAK-2: a phase IIA trial of the selective BRAF kinase inhibitor GSK2118436 in patients with BRAF mutation-positive (V600E/K) metastatic melanoma (abstr LBA1-1). Pigment Cell Res 2011;24:1020