The Role of BRAF/MEK Inhibition in Metastatic Malignant Melanoma – a Case Study

Česká verzia

Authors: J. Kopecký; O. Kubeček
Authors place of work: Klinika onkologie a radioterapie LF UK a FN Hradec Králové
Published in the journal: Klin Onkol 2016; 29(2): 133-138
Category: Kazuistika
doi: https://doi.org/10.14735/amko2016133

Metastazující maligní melanom se řadí mezi nádory s vysokou mortalitou. V posledních letech, díky poznání patogeneze maligního melanomu a vyvinutí léků cílených na tyto abnormality, jsme dosáhli významného posunu v léčbě našich pacientů. Hlavním přetrvávajícím nedostatkem těchto léků je vznik rezistence. Jedním ze způsobů, jak tuto rezistenci potlačit či alespoň oddálit, je použití kombinované terapie cílených léků.

Summary

Background:
Metastatic malignant melanoma belongs to a group of cancers with high mortality. In recent years, advances in our knowledge of the pathogenesis of melanoma and the discovery of new drugs has resulted in significant progress in the treatment of metastatic malignant melanoma patients. The development of resistance to these drugs, however, remains a challenge. One way how to avoid resistance, or at least delay it, is to administer combination therapy.

Observation and Conclusion:
This case study demonstrates that combination therapy with a BRAF and a MEK inhibitor can be used to successfully treat metastatic malignant melanoma patients and suggests they should be employed in therapeutic algorithms for patients with metastatic malignant melanoma and BRAF gene mutations.

Key words:
melanoma – dabrafenib – trametinib – BRAF inhibitor – MEK inhibitor

This work was supported by the grant SVV 2015-260286 and PRVOUK 37/06.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
10. 2. 2016

Accepted:
17. 2. 2016

Zdroje

1. Zvolský M. Vývoj incidence a mortality zhoubného melanomu v České republice v letech 1980– 2011 [monografie na internetu]. ÚZIS ČR, Aktuální informace č. 11/ 2014. Dostupné z: http://www.uzis.cz/node/6600.

2. Cheng Y, Zhang G, Li G. Targeting MAPK pathway in melanoma therapy. Cancer Metastasis Rev 2013; 32(3– 4): 567– 584. doi: 10.1007/s10555-013-9433-9.

3. 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(18): 1694– 1703. doi: 10.1056/NEJMoa1210093.

4. Long GV, Stroyakovskiy D, Gogas H et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3randomized controlled trial. Lancet 2015; 386(9992): 444– 451. doi: 10.1016/S0140-6736(15)60898-4.

5. Sosman JA, Kim KB, Schuchter L et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012; 366(8): 707– 714. doi: 10.1056/NEJMoa1112302.

6. Hodi FS, O’Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363(8): 711– 723. doi: 10.1056/NEJMoa1003466.

7. Robert C, Long GV, Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372(4): 320– 330. doi: 10.1056/NEJMoa1412082.

8. Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372(26): 2521– 2532. doi: 10.1056/NEJMoa1503093.

9. Ackerman A, Klein O, McDermott DF et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer 2014; 120(11): 1695– 1701. doi: 10.1002/cncr.28620.

10. Ascierto PA, Simeone E, Sileni VC 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– 149. doi: 10.3109/07357907.2014.885984.

11. Robert C, Ribas A, Wolchok JD et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomized dose-comparison cohort of a phase 1 trial. Lancet 2014; 384(9948): 1109– 1117. doi: 10.1016/S0140-6736(14)60958-2.

12. Topalian SL, Sznol M, McDermott DF et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32(10): 1020– 1030. doi: 10.1200/JCO.2013.53.0105.

13. ClinicalTrials.gov [homepage on the Internet]. A service of the U.S. National Institutes of Health [updated 2016 Feb 7; cited 2016 Feb 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT02224781.

14. Schadendorf D, Amonkar MM, Stroyakovskiy D et al. Health-related quality of life impact in a randomized phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma. Eur J Cancer 2015; 51(7): 833– 840. doi: 10.1016/j.ejca.2015.03.004.

15. Kopecký J, Kubeček O, Trojanová P et al. Adverse effects of modern treatment of malignant melanoma and their treatment/ management. Klin Onkol 2014; 27(6): 393– 400. doi: 10.14735/amko2014393.

16. 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– 114. doi: 10.1056/NEJMoa1203421.