Dabrafenib and Trametinib, alone and in combination for BRAF-Mutant metastatic melanoma

Clinical Cancer Research

Volumn 20, Issue 8, 2014, Pages 2035-2043

  Menzies, Alexander M ^a   Long, Georgina V ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; B RAF KINASE; DABRAFENIB; IMIDAZOLE DERIVATIVE; OXIME; PROTEIN KINASE INHIBITOR; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE; TRAMETINIB;

ANTAGONISTS AND INHIBITORS; BRAIN NEOPLASMS; CHEMICALLY INDUCED; DISEASE FREE SURVIVAL; FATIGUE; GENETICS; HUMAN; MELANOMA; MUTATION; PATHOLOGY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RASH; SECONDARY; TREATMENT OUTCOME;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BRAIN NEOPLASMS; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DISEASE-FREE SURVIVAL; EXANTHEMA; FATIGUE; HUMANS; IMIDAZOLES; MELANOMA; MUTATION; OXIMES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; PYRIDONES; PYRIMIDINONES; TREATMENT OUTCOME;

EID: 84898998810     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-2054     Document Type: Article

References (49)

1. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417: 949-54.
2. Long GV, Menzies AM, Nagrial AM, Haydu LE, Hamilton AL, Mann GJ, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol 2011;29: 1239-46.
3. Menzies AM, Haydu LE, Visintin L, Carlino MS, Howle JR, Thompson JF, et al. Distinguishing clinicopathologic features of patients with V600E and V600K BRAF-mutant metastatic melanoma. Clin Cancer Res 2012;18:3242-9.
4. Laquerre S, Arnone M, Moss K, Yang J, Fisher K, Kane-Carson LS, et al. A selective Raf kinase inhibitor induces cell death and tumor regression of human cancer cell lines encoding B-Raf V600E mutation [abstract]. Mol Cancer Ther 2009;8 Suppl 1:B88.
5. Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 2012;379:1893-901.
6. Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol 2013;31:3205-11.
7. Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, openlabel, phase 2 trial. Lancet Oncol 2012;13:1087-95.
8. Azer MW, Menzies AM, Haydu LE, Kefford RF, Long GV. Patterns of response and progression in patients with BRAF-mutant melanoma metastatic to the brain who were treated with dabrafenib. Cancer 2014;120:530-6.
9. Agarwala SS, Kirkwood JM, Gore M, Dreno B, Thatcher N, Czarnetski B, et al. Temozolomide for the treatment of brain metastases associated with metastatic melanoma: a phase II study. J Clin Oncol 2004;22:2101-7.
10. Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380:358-65.
11. Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. An update on BREAK-3, a phase III, randomized trial: dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM) [abstract]. J Clin Oncol 2013;31 Suppl:9013.
12. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507-16.
13. Chapman PB, Hauschild A, Robert C, Larkin JMG, Haanen JBAG, Ribas A, 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 Suppl:8502.
14. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010;363:809-19.
15. Kefford RF, Maio M, Arance A, Nathan P, Blank C, Avril MF, et al. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicenter study [abstract]. Pigment Cell Melanoma Res 2013;26 Suppl:965.
16. Dummer R, Goldinger SM, Turtschi CP, Eggmann NB, Michielin O, Mitchell L, et al. Vemurafenib in patients with BRAF mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study. Eur J Cancer 2013;50:611-21.
17. McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, et al. Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow- up of a phase 3, randomised, open-label study. Lancet Oncol 2014 Feb 6. [Epub ahead of print].
18. Klein O, Clements A, Menzies AM, O'Toole S, Kefford RF, Long GV. BRAF inhibitor activity in V600R metastatic melanoma. Eur J Cancer 2013;49:1073-9.
19. Bahadoran P, Allegra M, Le Duff F, Long-Mira E, Hofman P, Giacchero D, et al. Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma. J Clin Oncol. 2013;31:e324-6.
20. Menzies AM, Kefford RF, Long GV. Paradoxical oncogenesis: are all BRAF inhibitors equal? Pigment Cell Melanoma Res 2013;26: 611-5.
21. Dummer R, Rinderknecht J, Goldinger SM. Ultraviolet A and photosensitivity during vemurafenib therapy. N Engl J Med 2012;366: 480-1.
22. Dummer R, Robert C, Nyakas M, McArthur GA, Kudchadkar RR, Gomez-Roca C, et al. Initial results from a phase I, open-label, dose escalation study of the oral BRAF inhibitor LGX818 in patients with BRAF V600 mutant advanced or metastatic melanoma [abstract]. J Clin Oncol 31, 2013 (suppl; abstr 9028).
23. Gilmartin AG, Bleam MR, Groy A, Moss KG, Minthorn EA, Kulkarni SG, 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.
24. Infante JR, Fecher LA, Falchook GS, Nallapareddy S, Gordon MS, Becerra C, et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 doseescalation trial. Lancet Oncol 2012;13:773-81.
25. Falchook GS, Lewis KD, Infante JR, Gordon MS, Vogelzang NJ, Demarini DJ, et al. Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial. Lancet Oncol 2012;13:782-9.
26. Kim KB, Lewis K, Pavlick A, Infante JR, Ribas A, Sosman JA, 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 suppl LBA1-3:1021.
27. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012;367:107-14.
28. Schadendorf D, Flaherty KT, Hersey P, Nathan P, Garbe C, Milhem MM, et al. Overall survival (OS) update on METRIC (NCT01245062), a randomized phase 3 study to assess efficacy of trametinib (T) compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutation positive (+) advanced or metastatic melanoma (MM) [abstract]. Pigment Cell Melanoma Res 2013;26:997.
29. Kirkwood JM, Bastholt L, Robert C, Sosman J, Larkin J, Hersey P, 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.
30. Catalanotti F, Solit DB, Pulitzer MP, Berger MF, Scott SN, Iyriboz T, et al. Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY- 142886) in patients with BRAFV600E/K-mutated melanoma. Clin Cancer Res 2013;19:2257-64.
31. Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CML, Queirolo P, et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a nonrandomised, open-label phase 2 study. Lancet Oncol 2013;14: 249-56.
32. Robert C, Dummer R, Gutzmer R, Lorigan P, Kim KB, Nyakas M, et al. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. Lancet Oncol 2013; 14:733-40.
33. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23.
34. Ackerman A, Klein O,McDermott DF, Lawrence DP, Gunturi A, Flaherty KT, et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer. 2014 Feb 27. [Epub ahead of print].
35. Ascierto PA, Simeone E, Giannarelli D, Grimaldi AM, Romano A, Mozzillo N. Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J Transl Med 2012;10:107.
36. Amaravadi R, Kim K, Flaherty K, Chapman P, Puzanov I, Sosman J, et al. Prolonged responses to vemurafenib in patients with BRAFV600- mutant melanoma with low tumor burden at baseline. Pigment Cell Melanoma Res 2011;24:1024 (abstract P3).
37. Ribas A, Hodi FS, Callahan M, Konto C, Wolchok J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med 2013; 368:1365-6.
38. Kim KB, Kefford R, Pavlick AC, Infante JR, Ribas A, Sosman JA, 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;31:482-9.
39. Goldinger SM, Zimmer L, Schulz C, Ugurel S, Hoeller C, Kaehler KC, et al. Upstream mitogen-activated protein kinase (MAPK) pathway inhibition: MEK inhibitor followed by a BRAF inhibitor in advanced melanoma patients. Eur J Cancer 2014;50:406-10.
40. Shi H, Hugo W, Kong X, Hong A, Koya RC, Moriceau G, et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 2014;4:80-93.
41. Chan M, Haydu L, Menzies AM, Azer MWF, Klein O, Guminski A, et al. Clinical characteristics and survival of BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor dabrafenib or vemurafenib beyond disease progression [abstract]. J Clin Oncol 31, 2013 (suppl; abstr 9062).
42. Dahlman KB, Xia J, Hutchinson K, Ng C, Hucks D, Jia P, et al. BRAF (L597) mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov 2012;2:791-7.
43. Paraiso KH, Fedorenko IV, Cantini LP, Munko AC, Hall M, Sondak VK, et al. Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy. Br J Cancer 2010;102: 1724-30.
44. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 2012;367:1694-703.
45. Sosman JA, Daud A, Weber JS, Kim K, Kefford R, Flaherty K, et al. BRAF inhibitor (BRAFi) dabrafenib in combination with the MEK1/2 inhibitor (MEKi) trametinib in BRAFi-naive and BRAFi-resistant patients (pts) with BRAF mutation-positive metastatic melanoma (MM) [abstract]. J Clin Oncol 31, 2013 (suppl; abstr 9005).
46. Daud A, Weber J, Sosman J, Kim K, Gonzalez R, Hamid O, et al. Overall survival update for BRF113220 part C, a phase II three-arm randomized study of dabrafenib alone (D) vs. a combination of dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation- positive metastatic melanoma. The Society for Melanoma Research International Congress; 2013 Nov 17-20; Philadelphia (PA): 2013.
47. Menzies AM, Lee CI, Haydu LE, Azer MF, Clements A, Kefford RF, et al. Clinical correlates and management of pyrexia in patients (pts) treated with dabrafenib combined with trametinib (CombiDT) for V600 BRAFmutant metastatic melanoma [abstract]. Pigment Cell Melanoma Res 2012;25 Suppl 873.
48. Kefford R, Miller WH, Tan DS-W, Sullivan RJ, Long G, Dienstmann R, et al. Preliminary results from a phase Ib/II, open-label, doseescalation study of the oral BRAF inhibitor LGX818 in combination with the oral MEK1/2 inhibitor MEK162 in BRAF V600-dependent advanced solid tumors [abstract]. J Clin Oncol 31, 2013 (suppl; abstr 9029).
49. Daud A, Ribas A, Gonzalez R, Pavlick A, Hamid O, Puzanov I, et al. Phase 1B (BRIM7) results combining vemurafenib (VEM) and cobimetinib, a MEK inhibitor, in patients (pts) with advanced BRAFV600- mutated melanoma. The Society for Melanoma Research International Congress; 2013 Nov 17-20; Philadelphia (PA): 2013.