ISSN 2490-3329 (Print)
ISSN 2303-7954 (Online)

Volume 49, Issue 2, Article 8

(Scr Med 2018:49:126-131)
PROFESSIONAL ARTICLE

Analysis of Survival at Metastatic Melanoma Patients Treated with Vemurafenib - a Three Year Single Institution Study

Zdenka Gojković1, Dejan Ðokanović1, Branislava Jakovljević2, Siniša Maksimović3, Saša Jungić1, Ivanka Rakita1, Milka Vještica1, Radmila Rašeta1, Živko Vranješ1, Marina Štrbac1

1 Oncology Clinic, University Clinical Centre of the Republic of Srpska, Banja Luka, Republic of Srpska, Bosnia and Herzegovina
2 Hospital for Surgical and Internal Medicine S.tetik, Banja Luka, Republic of Srpska, Bosnia and Herzegovina
3 Surgery Department, General Hospital “Sveti Vračevi” Bijeljina, Republic of Srpska, Bosnia and Herzegovina
4 Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska, Bosnia and Herzegovina

 


DOI 10.7251/SCMED1802126G
UDC 616.5-006.81-085.65(497.6)
COBISS.RS-ID 7838232

 

ABSTRACT

Introduction: The introduction of BRAF inhibitor vemurafenib significantly improved overall survival (OS) in metastatic melanoma patients.

Aim of the Study: The purpose of this study was to determine OS and progression free survival (PFS) in patients with advanced metastatic melanoma treated with vemurafenib in the Oncology Clinic, University Clinical Centre of the Republic of Srpska (UKC RS). The secondary goal is to determine the effect of elevated serum lactate dehydrogenase (LDH) on OS.

Patients and Methods: We analysed patients that received vemurafenib in the April 2015. until March 2018. They had pathohistologically confirmed B-RAF positive metastatic melanoma. LDH values were measured at the start of the treatment.

Results: A total of 16 patients were analyzed, with an average age of 53 years (37-78). A large number of patients at the start had multiple sites of metastases. Calculated OS in patients who received vemurafenib is 11.8 months (p=0,23), with standard deviation (SD) 9.18. The calculated PFS is 9.5, SD 7,57. OS in patients with normal LDH is 14.4 months, SD 10.73, and with elevated LDH is 8.4 months, SD 4.9 (p=0.079).

Conclusion: Use of vemurafenib resulted in an improvement in PFS, with improved OS in patients with advanced BRAF-mutated melanoma. In patients with elevated LDH OS was reduced. This shows that LDH is a good prognostic marker and that we should do it routinely for all patients with melanoma. This study has indicated the need for new diagnostic and therapeutic options for melanoma in Republic of Srpska.

Key words: metastatic melanoma; BRAF mutation; vemurafenib

 

 

Pdf version of article

 


References:

1. MacKie RM, Hauschild A, Eggermont AM. Epidemiology of invasive cutaneous melanoma. Ann Oncol 2009;20:1-7.
2. Duncan LM. The classification of cutaneous melanoma. Hematol Oncol Clin North Am 2009;23:501-13.
3. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001;19:3622–34.
4. Eigentler TK, Caroli UM, Radny P, Garbe C. Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 2003;4:748–59.
5. 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.
6. 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.
7. 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.
8. 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.
9. Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 2006;24:4738–45.
10. Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, et al. Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 1999;17:2745–51.
11. 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.
12. Huncharek M, Caubet JF, McGarry R. Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials. Melanoma Res 2001;11:75–81.
13. Sasse AD, Sasse EC, Clark LG, Ulloa L, Clark OA. Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma. Cochrane Database Syst Rev 2007;1:CD005413.
14. Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Spatz A, et al. Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline - Update 2012. Eur J Cancer 2012;48:2375-90.
15. 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.
16. Chapman PB, Robert C, Larkin J, Haanen JB, Ribas A, Hogg D, et al. Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study. Ann Oncol 2017;28:2581-7.
17. Brochez L, Nćyćrt JM. Serological markers for melanoma. Br J Dermatol 2000;143:256–68.
18. Finck SJ, Giuliano ć, Morton DL. LDH and melanoma. Cancer 1983;51:840–3.
19. 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.
20. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014;371:1877–88.
21. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet 2015; 386: 444–51.
22. Ugurel S, Röhmel J, Ascierto PA, Flaherty KT, Grob JJ, Hauschild A, et al. Survival of patients with advanced metastatic melanoma: the impact of novel therapies. Eur J Cancer 2016;53:125-34.
23.Ugurel S, Röhmel J, Ascierto PA, Flaherty KT, Grob JJ, Hauschild A, et al. Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017. Eur J Cancer 2017;83:247–57.

 


Corresponding author:
Dejan Ðokanović,
e-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Manuscript received: May 5th, 2018
Manuscript accepted: November 27th, 2018