Encorafenib + binimetinib: a profile of their combined use in treating BRAF-mutated unresectable or metastatic melanoma
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Treatment with oral encorafenib (Braftovi®; a BRAF inhibitor) + binimetinib (Mektovi®; a MEK inhibitor) is a valuable addition to the options available to treat BRAF-mutated unresectable or metastatic melanoma in adults. The combination of encorafenib + binimetinib provided meaningful improvement with regard to progression-free survival, overall survival, clinical response and health-related quality of life relative to encorafenib and vemurafenib monotherapy in this patient population. The addition of binimetinib to encorafenib contributes to improving the efficacy and safety relative to encorafenib alone. Adverse events associated with encorafenib + binimetinib are manageable, with an overall tolerability profile largely consistent with those of other BRAF-MEK inhibitor combinations, but with some potential advantages with regard to pyrexia and photosensitivity. Adverse events that occur during encorafenib + binimetinib treatment can be managed with treatment adjustments.
The manuscript was reviewed by: G. Liszkay, Department of Oncodermatology, National Institute of Oncology, Budapest, Hungary, C. Robert, Département de Médecine Oncologique, Institute Gustave Roussy and Université Paris-Saclay, Villejuif, France; F. Vilchez-Márquez, Department of Dermatology, Hospital de Guadix, Guadix, Spain. During the peer review process, Pierre Fabre Médicament and Array BioPharma Inc., marketing-authorization holders of encorafenib and binimetinib, were also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with ethical standards
The preparation of this review was not supported by any external funding.
Conflict of interest
K. A. Lyseng-Williamson is an employee of Adis/Springer, is responsible for the article content and declares no conflicts of interest.
- 6.Braftovi (encorafenib) 50 and 75 mg hard capsules: EU prescribing information. Boulogne-Billancourt: Pierre Fabre Médicament; 2018.Google Scholar
- 7.Mektovi (binimetinib) 15 mg film-coated tablets: EU prescribing information. Boulogne-Billancourt: Pierre Fabre Médicament; 2018.Google Scholar
- 8.Braftovi® (encorafenib) capsules: US prescribing information. Boulder: Array BioPharma Inc.; 2018.Google Scholar
- 9.Mektovi® (binimetinib) tablets: US prescribing information. Boulder: Array BioPharma Inc.; 2018.Google Scholar
- 11.Sullivan RJ, Weber JS, Patel SP, et al. A phase Ib/I2 study of BRAF inhibitor (BRAFi) encorafenib (ENCO) plus MEK inhibitor (MEKi) binimetinib (BINI) in cutaneous melanoma patients naive to BRAFi treatment [abstract no. 9007 + slide presentation]. J Clin Oncol. 2015;33(15 Suppl).Google Scholar
- 14.Dummer R, Ascierto PA, Gogas H, et al. Results of COLUMBUS Part 2: a phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) versus ENCO in BRAF-mutant melanoma [abstract no. 1215O + slide presentation]. Ann Oncol. 2017;28(Suppl 5):v429–30.Google Scholar
- 15.Gogas H, Dummer R, Ascierto PA, et al. Quality-of-life (Qol) in COLUMBUS part 1: a phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) versus vemurafenib (VEM) or ENCO in braf-mutant melanoma [abstract no. 1245P + poster]. Ann Oncol. 2017;28(Suppl 5):442.Google Scholar
- 17.Arance A, Dummer R, Ascierto PA, et al. Hospitalization rates in COLUMBUS Part 1: a phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) versus vemurafenib (VEM) or ENCO in BRAF-mutant melanoma [abstract no. 1244P + poster]. Ann Oncol. 2017;28(Suppl 5):v441.Google Scholar
- 18.Tafinlar® (dabrafenib) capsules, for oral use: US prescribing information. East Hanover: Novartis Pharmaceutical Corporation; 2018.Google Scholar
- 22.National Comprehensive Cancer Network®. Clinical practice guidelines in oncology (NCCN Guidelines®): cutaneous melanoma (version 1.2019). Fort Washington: National Comprehensive Cancer Network® Inc.; 2018.Google Scholar
- 23.Smith AD. NICE OK for Bravtovi skin cancer drug; 2019. http://www.pharmatimes.com/news/nice_ok_for_bravtovi_skin_cancer_drug_1275652. Accessed 22 Jan 2019.
- 28.US National Institutes of Health. LGX818 and MEK162 in combination with a third agent (BKM120, LEE011, BGJ398 or INC280) in advanced BRAF melanoma [NCT02159066]. ClinicalTrials.gov; 2019. https://clinicaltrials.gov/ct2/show/NCT02159066. Accessed 22 Jan 2019.
- 29.US National Institutes of Health. Open label, multicentre study of encorafenib + binimetinib + PD (programmed cell death protein) -1 antibody pembrolizumab (IMMU-TARGET) [NCT02902042]. ClinicalTrials.gov; 2019. https://clinicaltrials.gov/ct2/show/NCT02902042. Accessed 22 Jan 2019.
- 30.US National Institutes of Health. Sequential combo immuno and target therapy (SECOMBIT) study [NCT02631447]. ClinicalTrials.gov; 2019. https://clinicaltrials.gov/ct2/show/NCT02631447. Accessed 22 Jan 2019.
- 31.US National Institutes of Health. Immunotherapy with ipilimumab and nivolumab preceded or not by a targeted therapy with encorafenib and binimetinib (EBIN) [NCT03235245]. ClinicalTrials.gov; 2019. https://clinicaltrials.gov/ct2/show/NCT03235245. Accessed 22 Jan 2019.