Trametinib: A novel signal transduction inhibitor for the treatment of metastatic cutaneous melanoma

American Journal of Health-System Pharmacy

Volumn 72, Issue 2, 2015, Pages 101-110

  Chung, Clement ^a   Reilly, Sean ^b  

^a Lyndon B Johnson General Hospital   (United States)

^b BEN TAUB GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; DABRAFENIB; MITOGEN ACTIVATED PROTEIN KINASE; RAF PROTEIN; RAS PROTEIN; TRAMETINIB; ANTINEOPLASTIC AGENT; PYRIDONE DERIVATIVE; PYRIMIDINONE DERIVATIVE;

ALOPECIA; ANGIOGENESIS; APOPTOSIS; AREA UNDER THE CURVE; CARDIOMYOPATHY; CELL INVASION; CELL PROLIFERATION; CELL SURVIVAL; CLINICAL TRIAL (TOPIC); CODON; CONSTIPATION; CROSS RESISTANCE; CUTANEOUS MELANOMA; DERMATITIS; DIARRHEA; DISEASE COURSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG COST; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG INDICATION; DRUG INHIBITION; DRUG SAFETY; ENZYME ACTIVATION; ENZYME INHIBITION; FATIGUE; FEVER; FOOD AND DRUG ADMINISTRATION; GENE EXPRESSION; GENE MUTATION; HEART EJECTION FRACTION; HUMAN; HYPERTENSION; MAXIMUM PLASMA CONCENTRATION; METASTATIC MELANOMA; MONOTHERAPY; MULTICENTER STUDY (TOPIC); NAUSEA; NONHUMAN; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PREGNANCY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RECOMMENDED DRUG DOSE; REVIEW; SIGNAL TRANSDUCTION; SKIN CARCINOMA; SKIN TOXICITY; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT RESPONSE; VOLUME OF DISTRIBUTION; VOMITING; ANIMAL; DRUG EFFECTS; MELANOMA; PHYSIOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; MAP KINASE SIGNALING SYSTEM; MELANOMA; PYRIDONES; PYRIMIDINONES; SIGNAL TRANSDUCTION;

EID: 84930165164     PISSN: 10792082     EISSN: 15352900     Source Type: Journal    
DOI: 10.2146/ajhp140045     Document Type: Review

References (49)

1. American Cancer Society. Cancer facts and figures 2014. www.cancer.gov/cancertopics/types/melanoma (accessed 2014 Apr 8).
2. Slingluff CL Jr, Flaherty K, Rosenberg SA et al. Cutaneous melanoma. In: Devita VT Jr, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's cancer: principles and practice of oncology. Philadelphia: Lippincott Williams & Wilkins; 2001:1646-52.
3. Lui P, Cashin R, Machado M et al. Treatments for metastatic melanoma: synthesis of evidence from randomized trials. Cancer Treat Rev. 2007; 33:665-80.
4. Eggermont AM, Schadendorf D. Melanoma and immunotherapy. Hematol Oncol Clin North Am. 2009; 23:547-64,ix-x.
5. Cheng Y, Zhang G, Li G. Targeting MAPK pathway in melanoma therapy. Cancer Metastasis Rev. 2013; 32:567-84.
6. 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; 3:6.
7. Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature. 2002; 417:949-54.
8. Mekinist (trametinib) prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2013 May.
9. Solit DB, Garraway LA, Pratilas CA et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature. 2006; 439:358-62.
10. Long GV, Menzies AM, Nagrial AM et al. Prognostic and clinicopathologic associations of oncogene BRAF in metastatic melanoma. J Clin Oncol. 2011; 29:1239-46.
11. Panka DJ, Atkins MB, Mier JW. Targeting the mitogen-activated protein kinase pathway in the treatment of malignant melanoma. Clin Cancer Res. 2006; 12:2371s-2375s.
12. Gray-Schopfer V, Wellbrock C, Marais R. Melanoma biology and new targeted therapy. Nature. 2007; 445:851-7.
13. Frémin C, Meloche S. From basic research to clinical development of MEK1/2 inhibitors for cancer therapy. J Hematol Oncol. 2010; 3:8.
14. Roberts PJ, Der CJ. Targeting the Raf- MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 2007; 26:3291-310.
15. Van Raamsdonk CD, Griewank KG, Crosby MB et al. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010; 363:2191.
16. Emery CM, Vijayendran KG, Zipser MC et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A. 2009; 106:20411-6.
17. Johannessen CM, Boehm JS, Kim SY et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010; 468:968-72.
18. 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.
19. Gowrishankar K, Snoyman S, Pupo GM et al. Acquired resistance to BRAF inhibition can confer cross-resistance to combined BRAF/MEK inhibition. J Invest Dermatol. 2012; 132:1850-9.
20. 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; 31:482-9.
21. 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.
22. 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.
23. Cox DS, Papadopoulos K, Fang L et al. Evaluation of the effects of food on the single-dose pharmacokinetics of trametinib, a first-in-class MEK inhibitor, in patients with cancer. J Clin Pharmacol. 2013; 53:946-54.
24. 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; 13:782-9.
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. ClinicalTrials.gov. A study comparing trametinib and dabrafenib combination therapy to dabrafenib monotherapy in subjects with BRAF-mutant melanoma. http://clinicaltrials.gov/show/NCT01584648 (accessed 2014 Apr 8).
27. Johnson DB, Sosman JA. Update on the targeted therapy of melanoma. Curr Treat Options Oncol. 2013; 14:280-92.
28. 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.
29. 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; 366:207-15.
30. Arnault JP, Mateus C, Escudier B et al. Skin tumors induced by sorafenib; paradoxic RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. Clin Cancer Res. 2012; 18:263-72.
31. Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011; 364:2507-16.
32. Red Book Online. Trametinib dimethyl-sulfoxide (Mekinist). www.micromedex solutions.com (accessed 2014 Apr 7).
33. Red Book Online. Dabrafenib mesylate (Tafinlar). www.micromedexsolutions.com (accessed 2014 Apr 7).
34. Jang S, Atkins MB. Which drug, and when, for patients with BRAF-mutant melanoma? Lancet Oncol. 2013; 14:e60-9.
35. Flanigan JC, Jilaveanu LB, Faries M et al. Melanoma brain metastases: is it time to reassess the bias? Curr Probl Cancer. 2011; 35:200-10.
36. Ascierto PA, Simerone 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.
37. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: Melanoma. V.4.2013. www.nccn.org (accessed 2014 Jan 1).
38. Ribas A, Hodi FS, Callahan M et al. Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med. 2013; 368:1365-6.
39. McArthur GA, Ribas A. Targeting oncogenic drivers and the immune system in melanoma. J Clin Oncol. 2013; 31:499-506.
40. ClinicalTrials.gov. A study of the BRAF inhibitor dabrafenib in combination with the MEK inhibitor trametinib in the adjuvant treatment of high-risk BRAF V600 mutation-positive melanoma after surgical resection (COMBI-AD). http://clinicaltrials.gov/ct2/show/NCT01682083?term=trametinib&rank=3 (accessed 2014 Jan 3).
41. ClinicalTrials.gov. Study of dabrafenib +/- trametinib in combination with ipilimumab for V600E/K mutation positive metastatic or unresectable melanoma. http://clinicaltrials.gov/ct2/show/NCT01767454?term=trametinib&rank=4 (accessed 2014 Jan 3).
42. 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; 366:2443-54.
43. 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; 366:2455-65.
44. Wolchok JD, Kluger H, Callahan MK et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013; 369:122-33.
45. Food and Drug Administration. Pembrolizumab. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm412861.htm (accessed 2014 Nov 12).
46. ClinicalTrials.gov. Trametinib, fluorouracil, and radiation therapy before surgery in treating patients with stage II-III rectal cancer. http://clinicaltrials.gov/ct2/show/NCT01740648?term=trametinib+and+rectal+cancer&rank=1 (accessed 2014 Jan 3).
47. ClinicalTrials.gov. Trametinib and Akt inhibitor GSK2141795 in treating patients with metastatic triple-negative breast cancer. http://clinicaltrials.gov/ct2/show/NCT01964924?term=trametinib+and+breast+cancer&rank=1 (accessed 2014 Jan 3).
48. ClinicalTrials.gov. A phase IIa study of the MEK inhibitor trametinib monotherapy in the treatment of biliary tract cancers. http://clinicaltrials.gov/ct2/show/NCT01943864?term=trametinib&rank=11 (accessed 2014 Jan 3).
49. ClinicalTrials.gov. Dabrafenib, trametinib, and navitoclax in treating patients with solid tumors that are metastatic or cannot be removed by surgery. http://clinicaltrials.gov/ct2/show/NCT01989585?term=trametinib&rank=12 (accessed 2014 Jan 3).