Vol 16, No 2 (2020)
Review paper
Published online: 2020-05-15

open access

Page views 1239
Article views/downloads 780
Get Citation

Connect on Social Media

Connect on Social Media

Encorafenib in combination with binimetinib — a new therapeutic option with a favourable safety profile in the treatment of patients with advanced BRAF mutation-positive melanoma

Paulina Jagodzińska-Mucha1, Piotr Rutkowski1
Oncol Clin Pract 2020;16(2):75-82.


Encorafenib and binimetinib were registered in 2018 for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. The results of the phase III study (Columbus) are very promising. Median PFS for patients who have received this treatment was 14.9 months, and the median OS was 33.6 months. The reduction of toxicity is the reason for the unique pharmacokinetic profile of this therapy. Knowledge about the adverse evets is important in the context of optimizing and individualizing treatment.

Article available in PDF format

View PDF Download PDF file


  1. Colombino M, Capone M, Lissia A, et al. BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. J Clin Oncol. 2012; 30(20): 2522–2529.
  2. Hamid O, Cowey CL, Offner M, et al. Efficacy, Safety, and Tolerability of Approved Combination BRAF and MEK Inhibitor Regimens for BRAF-Mutant Melanoma. Cancers (Basel). 2019; 11(11).
  3. Larkin J, Ascierto PA, Dréno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014; 371(20): 1867–1876.
  4. Delord JP, Robert C, Nyakas M, et al. Phase i dose-escalation and -expansion study of the BRAF inhibitor encorafenib (LGX818) in metastatic -mutant melanoma. Clin Cancer Res. 2017; 23(18): 5339–5348.
  5. Gogas HJ, Flaherty KT, Dummer R, et al. Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management. Eur J Cancer. 2019; 119: 97–106.
  6. Koelblinger P, Thuerigen O, Dummer R. Development of encorafenib for BRAF-mutated advanced melanoma. Curr Opin Oncol. 2018; 30(2): 125–133.
  7. Adelmann CH, Ching G, Du L, et al. Comparative profiles of BRAF inhibitors: the paradox index as a predictor of clinical toxicity. Oncotarget. 2016; 7(21): 30453–30460.
  8. Heinzerling L, Eigentler TK, Fluck M, et al. Tolerability of BRAF/MEK inhibitor combinations: adverse event evaluation and management. ESMO Open. 2019; 4(3): e000491.
  9. Ascierto P, McArthur G, Dréno B, et al. Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016; 17(9): 1248–1260.
  10. Dummer R, Ascierto PA, Gogas HJ, et al. Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018; 19(10): 1315–1327.
  11. Grob JJ, Amonkar MM, Karaszewska B, et al. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial. Lancet Oncol. 2015; 16(13): 1389–1398.
  12. Dréno B, Ribas A, Larkin J, et al. Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study. Ann Oncol. 2017; 28(5): 1137–1144.