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Update on advanced melanoma treatments: small molecule targeted therapy, immunotherapy, and future combination therapies

Zeitschrift:: Wiener Medizinische Wochenschrift > Ausgabe 13-14/2019

Autoren:: Andrew Kwong, Martina Sanlorenzo, Klemens Rappersberger, Igor Vujic

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Wichtige Hinweise

K. Rappersberger and I. Vujic contributed equally to the manuscript.

Summary

Early stage melanomas can achieve remarkable outcomes with surgery alone, but stage IV metastatic melanoma requires significant intervention and has poor outcomes. Here we present evidence on the latest advances in melanoma treatment, discuss the scientific concepts behind new therapies, and analyze the potential of future treatment combinations.

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Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA. Increasing burden of melanoma in the United States. J Invest Dermatol. 2009;129:1666–74. CrossRefPubMedPubMedCentral

Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF. et al. SEER Cancer Statistics Review (CSR) 1975–2011. Bethesda: National Cancer Institute; 2014.

Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ. Early detection and treatment of skin cancer. Am Fam Physician. 2000;62:357–68, 375–6, 381–2. PubMed

Balch CM, Gershenwald JE, Soong S‑J, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199–206. CrossRefPubMedPubMedCentral

Menzies AM, Long GV, Murali R. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Devel Ther. 2012;6:391–405. PubMedPubMedCentral

Avril MF, Aamdal S, Grob JJ, Hauschild A, Mohr P, Bonerandi JJ, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004;22:1118–25. CrossRef

Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, 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. CrossRefPubMed

Hauschild A, Agarwala SS, Trefzer U, Hogg D, Robert C, Hersey P, 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;27:2823–30. CrossRefPubMed

Sanlorenzo M, Vujic I, Posch C, Dajee A, Yen A, Kim S, et al. Melanoma immunotherapy. Cancer Biol Ther. 2014;15:665–74. CrossRefPubMedPubMedCentral

10.

Mekhail T, Wood L, Bukowski R. Interleukin-2 in cancer therapy: uses and optimum management of adverse effects. BioDrugs. 2000;14(5):299–318. CrossRefPubMed

11.

Jarkowski A, Norris L, Trinh VA. Controversies in the management of advanced melanoma: “Gray” areas amid the “black and blue”. Ann Pharmacother. 2014;48:1456–68. CrossRefPubMed

12.

National Cancer Institute. Targeted cancer therapies 2014. http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted. Accessed 11 Nov 2014.

13.

Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353:2135–47. CrossRefPubMed

14.

Colombino M, Lissia A, Capone M, De Giorgi V, Massi D, Stanganelli I, et al. Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma. J Transl Med. 2013;11:202. CrossRefPubMedPubMedCentral

15.

Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7:295–308. CrossRefPubMed

16.

Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989;49(17):4682–9. PubMed

17.

Repasky GA, Chenette EJ, Der CJ. Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis? Trends Cell Biol. 2004;14:639–47. CrossRefPubMed

18.

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. CrossRefPubMed

19.

Luke JJ, Ott PA. New developments in the treatment of metastatic melanoma – role of dabrafenib-trametinib combination therapy. Drug Healthc Patient Saf. 2014;6:77–88. CrossRefPubMedPubMedCentral

20.

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. CrossRefPubMed

21.

Joseph EW, Pratilas CA, Poulikakos PI, Tadi M, Wang W, Taylor BS, et al. The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner. Proc Natl Acad Sci USA. 2010;107:14903–8. CrossRefPubMedPubMedCentral

22.

Rahman MA, Salajegheh A, Smith RA, Lam AK-Y. BRAF inhibitors: from the laboratory to clinical trials. Crit Rev Oncol Hematol. 2014;90:220–32. CrossRefPubMed

23.

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. CrossRefPubMedPubMedCentral

24.

National Cancer Institute. FDA approval for Vemurafenib 2013. http://www.cancer.gov/cancertopics/druginfo/fda-vemurafenib. Accessed 11 Oct 2014.

25.

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. J Clin Oncol. 2012;30(Suppl):abstr 8502^, http://meetinglibrary.asco.org/content/97795-114. Accessed 11 Nov 2014.

26.

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;15:323–32. CrossRefPubMedPubMedCentral

27.

Larkin J, Del Vecchio M, Ascierto PA, Krajsova I, Schachter J, Neyns B, et al. Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol. 2014;15:436–44. CrossRefPubMed

28.

Hauschild A, Grob J‑J, 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. CrossRefPubMed

29.

Food and Drug Administration. Research C for DE and. Approved drugs – Dabrafenib 2014. http://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm354477.htm. Accessed 12 Oct 2014.

30.

Hauschild A, Grobb J, Demidov L, Jouary T, Gutzmer R, Millward M, et al. An update on overall survival (os) and follow-on therapies in break-3, a phase iii, randomized trial: Dabrafenib (d) vs. Dacarbazine (dtic) in patients (pts) with Braf V600e mutation-positive metastatic melanoma (mm). Ann Oncol. 2014;25:iv378. CrossRef

31.

Beale S, Dickson R, Bagust A, Blundell M, Dundar Y, Boland A, et al. Vemurafenib for the treatment of locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma: a NICE single technology appraisal. Pharmacoeconomics. 2013;31:1121–9. CrossRefPubMed

32.

Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, et al. Survival in BRAF V600–mutant advanced melanoma treated with Vemurafenib. N Engl J Med. 2012;366:707–14. CrossRefPubMedPubMedCentral

33.

Karimkhani C, Gonzalez R, Dellavalle RP. A review of novel therapies for melanoma. Am J Clin Dermatol. 2014;15:323–37. CrossRefPubMed

34.

Hu-Lieskovan S, Robert L, Homet Moreno B, Ribas A. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol. 2014;32:2248–54. CrossRefPubMedPubMedCentral

35.

Trunzer K, Pavlick AC, Schuchter L, Gonzalez R, McArthur GA, Hutson TE, et al. Pharmacodynamic effects and mechanisms of resistance to Vemurafenib in patients with metastatic melanoma. J Clin Oncol. 2013;31:1767–74. CrossRefPubMed

36.

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. CrossRefPubMed

37.

Van Allen EM, Wagle N, Sucker A, Treacy DJ, Johannessen CM, Goetz EM, et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov. 2014;4:94–109. CrossRefPubMed

38.

Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, et al. Melanomas acquire resistance to B‑RAF(V600E) inhibition by RTK or N‑RAS upregulation. Nature. 2010;468:973–7. CrossRefPubMedPubMedCentral

39.

Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011;29:3085–96. CrossRefPubMedPubMedCentral

40.

Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, Johnson LA, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010;468:968–72. CrossRefPubMedPubMedCentral

41.

Shi H, Moriceau G, Kong X, Lee M‑K, Lee H, Koya RC, et al. Melanoma whole-exome sequencing identifies V600EB-RAF amplification-mediated acquired B‑RAF inhibitor resistance. Nat Commun. 2012;3:724. CrossRefPubMedPubMedCentral

42.

Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011;480:387–90. CrossRefPubMedPubMedCentral

43.

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;464:427–30. CrossRefPubMedPubMedCentral

44.

Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature. 2010;464:431–5. CrossRefPubMed

45.

Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell. 2010;140:209–21. CrossRefPubMedPubMedCentral

46.

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. CrossRefPubMed

47.

Food and Drug Administration. Research C for DE and. Approved drugs – Trametinib 2014. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm354478.htm. Accessed 14 Oct 2014.

48.

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. CrossRefPubMed

49.

Grazia G, Penna I, Perotti V, Anichini A, Tassi E. Towards combinatorial targeted therapy in melanoma: from pre-clinical evidence to clinical application (review). Int J Oncol. 2014;45:929–49. CrossRefPubMedPubMedCentral

50.

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. CrossRefPubMedPubMedCentral

51.

Food and Drug Administration. Research C for DE and. Approved drugs – Trametinib and Dabrafenib 2014. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm381451.htm. Accessed 14 Oct 2014.

52.

Long GV, Stroyakovsky DL, Gogas H, Levchenko E, de Braud F, Larkin JMG, et al. COMBI-d: a randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAFV600E/K mutation-positive cutaneous melanoma. J Clin Oncol. 2014;32(S7):5–12, http://meetinglibrary.asco.org/content/128598-144. Accessed 14 Oct 2014.

53.

Sanlorenzo M, Choudhry A, Vujic I, Posch C, Chong K, Johnston K, et al. Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma. J Am Acad Dermatol. 2014;71:1102–1109.e1. CrossRefPubMedPubMedCentral

54.

Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9. CrossRefPubMed

55.

Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867–76. CrossRefPubMed

56.

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. CrossRefPubMedPubMedCentral

57.

Food and Drug Administration. Press Announcements – FDA approves new treatment for a type of late-stage skin cancer 2011. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm1193237.htm. Accessed 24 Oct 2014.

58.

Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from phase II and phase III trials of Ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33(17):1889–94. doi: 10.1200/jco.2014.56.2736. CrossRefPubMedPubMedCentral

59.

Hamid O, Robert C, Daud A, Hodi FS, Hwu W‑J, Kefford R, et al. Safety and tumor responses with Lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134–44. CrossRefPubMedPubMedCentral

60.

Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384:1109–17. CrossRefPubMed

61.

Food and Drug Administration. Research C for DE and. Approved drugs – Pembrolizumab 2014. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm412861.htm. Accessed 25 Oct 2014.

62.

Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, et al. Association of Pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315:1600–9. CrossRefPubMed

63.

Weber JS, Minor DR, D’Angelo S, Hodi FS, Gutzmer R, Neyns B. et al. A phase 3 randomized, open-label study of Nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus investigator’s choice chemotherapy (ICC) in patients with advanced melanoma after prior anti-CTLA-4 therapy. ESMO Conference, Madrid. 2014. CrossRef

64.

Food and Drug Administration. Press announcements – FDA approves Opdivo for advanced melanom 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427716.htm. Accessed 24 Dec 2014.

65.

Ott PA, Hodi FS, Robert C. CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic modalities with durable clinical benefit in melanoma patients. Clin Cancer Res. 2013;19:5300–9. CrossRefPubMed

66.

Sznol M, Kluger HM, Callahan MK, Postow MA, Gordon RA, Segal NH, et al. Survival, response duration, and activity by BRAF mutation (MT) status of Nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and Iipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). J Clin Oncol. 2014;32:5s, http://meetinglibrary.asco.org/content/126008-144. Accessed 6 Nov 2014. CrossRef

67.

Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus Ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–33. CrossRefPubMedPubMedCentral

68.

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34. CrossRefPubMedPubMedCentral

69.

Weber JS, Gibney G, Sullivan RJ, Sosman JA, Slingluff CL, Lawrence DP, et al. Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. Lancet Oncol. 2016;17(7):943–55. doi: 10.1016/s1470-2045(16)30126-7. CrossRefPubMedPubMedCentral

70.

Girotti MR, Saturno G, Lorigan P, Marais R. No longer an untreatable disease: How targeted and immunotherapies have changed the management of melanoma patients. Mol Oncol. 2014;8:1140–58. CrossRefPubMedPubMedCentral

71.

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. CrossRefPubMed

72.

Ackerman A, Klein O, McDermott DF, Wang W, Ibrahim N, Lawrence DP, et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer. 2014;120:1695–701. CrossRefPubMed

73.

Ascierto PA, Simeone E, Sileni VC, Del Vecchio M, Marchetti P, Cappellini GCA, et al. Sequential treatment with Ipilimumab and BRAF inhibitors in patients with metastatic melanoma: data from the Italian cohort of the Ipilimumab expanded access program. Cancer Invest. 2014;32:144–9. CrossRefPubMed

74.

Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, Ferrone CR, et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 2013;19:1225–31. CrossRefPubMedPubMedCentral

75.

Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, et al. Selective BRAF inhibitors induce marked T‑cell infiltration into human metastatic melanoma. Clin Cancer Res. 2012;18:1386–94. CrossRefPubMed

76.

Callahan MK, Masters G, Pratilas CA, Ariyan C, Katz J, Kitano S, et al. Paradoxical activation of T cells via augmented ERK signaling mediated by a RAF inhibitor. Cancer Immunol Res. 2014;2:70–9. CrossRefPubMed

Titel: Update on advanced melanoma treatments: small molecule targeted therapy, immunotherapy, and future combination therapies
Autoren:: Andrew Kwong
Martina Sanlorenzo
Klemens Rappersberger
Igor Vujic
Publikationsdatum: 13.01.2017
DOI: https://doi.org/10.1007/s10354-016-0535-1
Verlag: Springer Vienna
Zeitschrift: Wiener Medizinische Wochenschrift
Ausgabe 13-14/2019
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X

Springer Medizin Österreich

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