COLUMBUS 5-Year Update: A Randomized, Open-Label, Phase III Trial of Encorafenib Plus Binimetinib Versus Vemurafenib or Encorafenib in Patients With BRAF V600-Mutant Melanoma

Reinhard Dummer, Keith T Flaherty, Caroline Robert, Ana Arance, Jan Willem B de Groot, Claus Garbe, Helen J Gogas, Ralf Gutzmer, Ivana Krajsová, Gabriella Liszkay, Carmen Loquai, Mario Mandalà, Dirk Schadendorf, Naoya Yamazaki, Alessandra di Pietro, Jean Cantey-Kiser, Michelle Edwards, Paolo A Ascierto, Reinhard Dummer, Keith T Flaherty, Caroline Robert, Ana Arance, Jan Willem B de Groot, Claus Garbe, Helen J Gogas, Ralf Gutzmer, Ivana Krajsová, Gabriella Liszkay, Carmen Loquai, Mario Mandalà, Dirk Schadendorf, Naoya Yamazaki, Alessandra di Pietro, Jean Cantey-Kiser, Michelle Edwards, Paolo A Ascierto

Abstract

Purpose: Combination treatment with BRAF and MEK inhibitors has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is a standard of care for the treatment of advanced BRAF V600-mutant melanoma. Here, we report the 5-year update from the COLUMBUS trial (ClinicalTrials.gov identifier: NCT01909453).

Methods: Patients with locally advanced unresectable or metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, vemurafenib 960 mg twice daily, or encorafenib 300 mg once daily. An updated analysis was conducted 65 months after the last patient was randomly assigned.

Results: Five hundred seventy-seven patients were randomly assigned: 192 to encorafenib plus binimetinib, 191 to vemurafenib, and 194 to encorafenib. The 5-year PFS and OS rates with encorafenib plus binimetinib were 23% and 35% overall and 31% and 45% in those with normal lactate dehydrogenase levels, respectively. In comparison, the 5-year PFS and OS rates with vemurafenib were 10% and 21% overall and 12% and 28% in those with normal lactate dehydrogenase levels, respectively. The median duration of response with encorafenib plus binimetinib was 18.6 months, with disease control achieved in 92.2% of patients. In comparison, the median duration of response with vemurafenib was 12.3 months, with disease control achieved in 81.2% of patients. Long-term follow-up showed no new safety concerns, and results were consistent with the known tolerability profile of encorafenib plus binimetinib. Interactive visualization of the data presented in this article is available at COLUMBUS dashboard.

Conclusion: In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with BRAF V600-mutant melanoma.

Conflict of interest statement

Reinhard Dummer

Honoraria: Roche, Novartis, Bristol Myers Squibb, MSD, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, CatalYm, Second Genome, Regeneron, Alligator Bioscience, MaxiVax, touchIME, T3 Pharmaceuticals, Pfizer

Consulting or Advisory Role: Roche, Bristol Myers Squibb, MSD, Novartis, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, CatalYm, Second Genome, Alligator Bioscience, touchIME, MaxiVax, Regeneron, Pfizer, T3 Pharmaceuticals

Research Funding: Roche (Inst), Bristol Myers Squibb (Inst), Novartis (Inst), MSD (Inst), Amgen (Inst)

Keith T. Flaherty

Stock and Other Ownership Interests: Clovis Oncology, Loxo, X4 Pharma, Strata Oncology, PIC Therapeutics, Apricity Health, Oncoceutics, FogPharma, Tvardi Therapeutics, Checkmate Pharmaceuticals, Kinnate Biopharma, Scorpion Therapeutics, ALX Oncology, xCures, Monopteros Therapeutics, Vibliome Therapeutics, Transcode Therapeutics, Soley Therapeutics, Nextech Invest

Consulting or Advisory Role: Novartis, Lilly, Oncoceutics, Tvardi Therapeutics, Takeda, Debiopharm Group

Caroline Robert

Stock and Other Ownership Interests: Ribonexus

Consulting or Advisory Role: Bristol Myers Squibb, Roche, Novartis, Pierre Fabre, MSD, Sanofi, AstraZeneca, Pfizer

Research Funding: Novartis (Inst)

Ana Arance

Consulting or Advisory Role: BMS, Roche, Novartis, Pierre Fabre, MSD, Merck, Sanofi

Speakers' Bureau: Pierre Fabre, Novartis, MSD, BMS, Roche, Merck, Sanofi

Research Funding: Pierre Fabre (Inst), Novartis (Inst), Roche (Inst), BMS (Inst), MSD (Inst), Merck (Inst), Sanofi (Inst)

Travel, Accommodations, Expenses: BMS, MSD, Novartis, Pierre Fabre

Jan Willem B. de Groot

Consulting or Advisory Role: Bristol Myers Squibb, Pierre Fabre, Servier

Claus Garbe

Honoraria: BMS, MSD Oncology, NeraCare GmbH, Novartis, Philogen, Roche/Genentech, Sanofi, CeCaVa

Consulting or Advisory Role: BMS, MSD Oncology, NeraCare GmbH, Novartis, Philogen, Roche/Genentech, Sanofi, CeCaVa

Research Funding: BMS (Inst), Novartis (Inst), NeraCare GmbH (Inst), Roche/Genentech (Inst)

Helen J. Gogas

Honoraria: Bristol Myers Squibb, MSD Oncology, Pierre Fabre, Sanofi/Regeneron

Consulting or Advisory Role: Bristol Myers Squibb, MSD Oncology, Amgen, Pierre Fabre, Sanofi/Regeneron

Research Funding: Bristol Myers Squibb (Inst), Roche (Inst), MSD Oncology (Inst), Amgen (Inst), Novartis (Inst), Iovance Biotherapeutics (Inst)

Travel, Accommodations, Expenses: Bristol Myers Squibb, MSD, Amgen, Pfizer

Ralf Gutzmer

Honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Novartis, Merck Serono, Almirall Hermal GmbH, Amgen, Sun Pharma, Pierre Fabre, Sanofi/Regeneron, Immunocore

Consulting or Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Novartis, Almirall Hermal GmbH, 4SC, Amgen, Pierre Fabre, Merck Serono, Sun Pharma, Sanofi, Immunocore

Research Funding: Pfizer (Inst), Novartis (Inst), Johnson & Johnson (Inst), Amgen (Inst), Merck Serono (Inst), Sun Pharma (Inst), Sanofi (Inst)

Travel, Accommodations, Expenses: Bristol Myers Squibb, Roche, Merck Serono, Pierre Fabre, Sun Pharma

Gabriella Liszkay

Consulting or Advisory Role: Roche, MSD, Novartis, Bristol Myers Squibb/Pfizer, Sanofi, Pfizer

Speakers' Bureau: Bristol Myers Squibb, MSD Oncology (Inst), Sanofi

Research Funding: Roche, Novartis (Inst), Inscite Corporation (Inst)

Carmen Loquai

Consulting or Advisory Role: Bristol Myers Squibb (Inst), MSD (Inst), BioNTech (Inst), Novartis (Inst), Sanofi (Inst), Pierre Fabre (Inst), Almirall Hermal GmbH (Inst), Sun Pharma (Inst), Merck (Inst), Roche (Inst), Kyowa Kirin International (Inst)

Travel, Accommodations, Expenses: Bristol Myers Squibb (Inst), MSD (Inst), BioNTech (Inst), Novartis (Inst), Sanofi (Inst), Pierre Fabre (Inst), Almirall Hermal GmbH (Inst), Sun Pharma (Inst), Merck (Inst), Roche (Inst), Kyowa Kirin International (Inst)

Mario Mandalà

Honoraria: MSD Oncology, Novartis, Pierre Fabre, Sanofi/Aventis, Bristol Myers Squibb/Sanofi

Consulting or Advisory Role: Bristol Myers Squibb, MSD Oncology, Novartis, Pierre Fabre

Research Funding: Novartis (Inst)

Dirk Schadendorf

Honoraria: Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Immunocore, Merck Serono, Array BioPharma, Pfizer, Pierre Fabre, Philogen, Regeneron, 4SC, Sanofi/Regeneron, NeraCare GmbH, Sun Pharma, Inflarx GmbH, Ultimovacs, Sandoz, Amgen, Daiichi Sankyo Japan, LabCorp, Nektar, Replimune

Consulting or Advisory Role: Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, 4SC, Pierre Fabre, Sanofi/Regeneron, Nektar

Speakers' Bureau: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi/Regeneron, Merck KGaA

Research Funding: Bristol Myers Squibb (Inst), Novartis (Inst), Roche (Inst), MSD Oncology (Inst), Array BioPharma/Pfizer (Inst), Amgen (Inst)

Travel, Accommodations, Expenses: Roche/Genentech, Bristol Myers Squibb, Merck Serono, Novartis, Merck Sharp & Dohme, Pierre Fabre, Sanofi/Regeneron

Naoya Yamazaki

Consulting or Advisory Role: Ono Pharmaceutical, Chugai Pharma, MSD

Speakers' Bureau: Ono Pharmaceutical, Bristol Myers Squibb Japan, Novartis, MSD

Research Funding: Ono Pharmaceutical (Inst), Bristol Myers Squibb Japan (Inst), Novartis (Inst), Astellas Amgen BioPharma (Inst), Merck Serono (Inst), Takara Bio (Inst)

Alessandra di Pietro

Stock and Other Ownership Interests: Pfizer

Honoraria: Pfizer

Jean Cantey-Kiser

Employment: PharPoint Research

Michelle Edwards

Employment: Arvinas, Pfizer, Merck

Stock and Other Ownership Interests: Arvinas, Merck

Paolo A. Ascierto

Stock and Other Ownership Interests: PrimeVax

Consulting or Advisory Role: Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Array BioPharma, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Takis Biotech, Lunaphore Technologies, Seattle Genetics, ITeos Therapeutics, Medicenna, Bio-Al Health

Research Funding: Bristol Myers Squibb (Inst), Roche/Genentech (Inst), Array BioPharma (Inst), Sanofi (Inst)

Travel, Accommodations, Expenses: Merck Sharp & Dohme

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
PFS in (A) all patients, (B) patients in the encorafenib plus binimetinib arm according to baseline LDH levels, and (C) patients in the encorafenib plus binimetinib arm who had a low tumor burden (ie, normal LDH levels and

FIG 2.

OS in (A) all patients,…

FIG 2.

OS in (A) all patients, (B) patients in the encorafenib plus binimetinib arm…

FIG 2.
OS in (A) all patients, (B) patients in the encorafenib plus binimetinib arm according to baseline LDH levels, and (C) patients in the encorafenib plus binimetinib arm who had a low tumor burden (ie, normal LDH levels and

FIG 3.

(A) OS in subgroups for…

FIG 3.

(A) OS in subgroups for encorafenib plus binimetinib versus vemurafenib. The Cox proportional…

FIG 3.
(A) OS in subgroups for encorafenib plus binimetinib versus vemurafenib. The Cox proportional hazards model is unstratified. (B) Proportion of patients treated with encorafenib plus binimetinib by duration of response. AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LDH, lactate dehydrogenase; OS, overall survival.

FIG A1.

CONSORT diagram. a Some patients…

FIG A1.

CONSORT diagram. a Some patients were ineligible for more than one reason. b…

FIG A1.
CONSORT diagram. aSome patients were ineligible for more than one reason. bPrimary reason. cOngoing at the time of data cutoff (September 15, 2020). AE, adverse event.

FIG A2.

OS in subgroups for encorafenib…

FIG A2.

OS in subgroups for encorafenib plus binimetinib versus encorafenib. The Cox proportional hazards…

FIG A2.
OS in subgroups for encorafenib plus binimetinib versus encorafenib. The Cox proportional hazards model is unstratified. AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LDH, lactate dehydrogenase; OS, overall survival.

FIG A3.

(A) PFS in the encorafenib…

FIG A3.

(A) PFS in the encorafenib plus binimetinib arm by response status at 6…

FIG A3.
(A) PFS in the encorafenib plus binimetinib arm by response status at 6 months. (B) OS in the encorafenib plus binimetinib arm by response status at 6 months. Patients are classified on the basis of their response status at 6 months (the landmark time). The number of patients at risk at baseline excludes patients who had an event or were censored at 6 months. HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
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References
    1. Krauthammer M, Kong Y, Bacchiocchi A, et al. : Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nat Genet 47:996-1002, 2015 - PMC - PubMed
    1. Davies H, Bignell GR, Cox C, et al. : Mutations of the BRAF gene in human cancer. Nature 417:949-954, 2002 - PubMed
    1. Seth R, Messersmith H, Kaur V, et al. : Systemic therapy for melanoma: ASCO guideline. J Clin Oncol 38:3947-3970, 2020 - PubMed
    1. Michielin O, van Akkooi ACJ, Ascierto PA, et al. : Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 30:1884-1901, 2019 - PubMed
    1. Keilholz U, Ascierto PA, Dummer R, et al. : ESMO consensus conference recommendations on the management of metastatic melanoma: Under the auspices of the ESMO Guidelines Committee. Ann Oncol 31:1435-1448, 2020 - PubMed
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FIG 2.
FIG 2.
OS in (A) all patients, (B) patients in the encorafenib plus binimetinib arm according to baseline LDH levels, and (C) patients in the encorafenib plus binimetinib arm who had a low tumor burden (ie, normal LDH levels and

FIG 3.

(A) OS in subgroups for…

FIG 3.

(A) OS in subgroups for encorafenib plus binimetinib versus vemurafenib. The Cox proportional…

FIG 3.
(A) OS in subgroups for encorafenib plus binimetinib versus vemurafenib. The Cox proportional hazards model is unstratified. (B) Proportion of patients treated with encorafenib plus binimetinib by duration of response. AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LDH, lactate dehydrogenase; OS, overall survival.

FIG A1.

CONSORT diagram. a Some patients…

FIG A1.

CONSORT diagram. a Some patients were ineligible for more than one reason. b…

FIG A1.
CONSORT diagram. aSome patients were ineligible for more than one reason. bPrimary reason. cOngoing at the time of data cutoff (September 15, 2020). AE, adverse event.

FIG A2.

OS in subgroups for encorafenib…

FIG A2.

OS in subgroups for encorafenib plus binimetinib versus encorafenib. The Cox proportional hazards…

FIG A2.
OS in subgroups for encorafenib plus binimetinib versus encorafenib. The Cox proportional hazards model is unstratified. AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LDH, lactate dehydrogenase; OS, overall survival.

FIG A3.

(A) PFS in the encorafenib…

FIG A3.

(A) PFS in the encorafenib plus binimetinib arm by response status at 6…

FIG A3.
(A) PFS in the encorafenib plus binimetinib arm by response status at 6 months. (B) OS in the encorafenib plus binimetinib arm by response status at 6 months. Patients are classified on the basis of their response status at 6 months (the landmark time). The number of patients at risk at baseline excludes patients who had an event or were censored at 6 months. HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
FIG 3.
FIG 3.
(A) OS in subgroups for encorafenib plus binimetinib versus vemurafenib. The Cox proportional hazards model is unstratified. (B) Proportion of patients treated with encorafenib plus binimetinib by duration of response. AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LDH, lactate dehydrogenase; OS, overall survival.
FIG A1.
FIG A1.
CONSORT diagram. aSome patients were ineligible for more than one reason. bPrimary reason. cOngoing at the time of data cutoff (September 15, 2020). AE, adverse event.
FIG A2.
FIG A2.
OS in subgroups for encorafenib plus binimetinib versus encorafenib. The Cox proportional hazards model is unstratified. AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; LDH, lactate dehydrogenase; OS, overall survival.
FIG A3.
FIG A3.
(A) PFS in the encorafenib plus binimetinib arm by response status at 6 months. (B) OS in the encorafenib plus binimetinib arm by response status at 6 months. Patients are classified on the basis of their response status at 6 months (the landmark time). The number of patients at risk at baseline excludes patients who had an event or were censored at 6 months. HR, hazard ratio; OS, overall survival; PFS, progression-free survival.

References

    1. Krauthammer M, Kong Y, Bacchiocchi A, et al. : Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas. Nat Genet 47:996-1002, 2015
    1. Davies H, Bignell GR, Cox C, et al. : Mutations of the BRAF gene in human cancer. Nature 417:949-954, 2002
    1. Seth R, Messersmith H, Kaur V, et al. : Systemic therapy for melanoma: ASCO guideline. J Clin Oncol 38:3947-3970, 2020
    1. Michielin O, van Akkooi ACJ, Ascierto PA, et al. : Cutaneous melanoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 30:1884-1901, 2019
    1. Keilholz U, Ascierto PA, Dummer R, et al. : ESMO consensus conference recommendations on the management of metastatic melanoma: Under the auspices of the ESMO Guidelines Committee. Ann Oncol 31:1435-1448, 2020
    1. Michielin O, van Akkooi A, Lorigan P, et al. : ESMO consensus conference recommendations on the management of locoregional melanoma: Under the auspices of the ESMO Guidelines Committee. Ann Oncol 31:1449-1461, 2020
    1. National Comprehensive Cancer Network : NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Cutaneous Melanoma (Version 3.2022). , 2022
    1. Robert C, Grob JJ, Stroyakovskiy D, et al. : Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med 381:626-636, 2019
    1. Ascierto PA, Dreno B, Larkin J, et al. : 5-year outcomes with cobimetinib plus vemurafenib in BRAF (V600) mutation-positive advanced melanoma: Extended follow-up of the coBRIM study. Clin Cancer Res 27:5225-5235, 2021
    1. Sullivan RJ, Weber J, Patel S, et al. : A phase Ib/II study of the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with BRAFV600E/K-mutant solid tumors. Clin Cancer Res 26:5102-5112, 2020
    1. Dummer R, Ascierto PA, Gogas HJ, et al. : Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol 19:603-615, 2018
    1. 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, Presented at 42nd Annual Congress of the European Society for Medical Oncology, Madrid, Spain, September 8-12, 2017 (abstr 1215O)
    1. Koelblinger P, Thuerigen O, Dummer R: Development of encorafenib for BRAF-mutated advanced melanoma. Curr Opin Oncol 30:125-133, 2018
    1. Holderfield M, Merritt H, Chan J, et al. : RAF inhibitors activate the MAPK pathway by relieving inhibitory autophosphorylation. Cancer Cell 23:594-602, 2013
    1. Stuart DD, Li N, Poon DJ, et al. : Preclinical profile of LGX818: A potent and selective RAF kinase inhibitor, Presented at 103rd Annual Meeting of the American Association for Cancer Research, Chicago, IL, March 31-April 4, 2012 (abstr 3790)
    1. Delord JP, Robert C, Nyakas M, et al. : Phase I dose-escalation and -expansion study of the BRAF inhibitor encorafenib (LGX818) in metastatic BRAF-mutant melanoma. Clin Cancer Res 23:5339-5348, 2017
    1. Ascierto PA, Schadendorf D, Berking C, et al. : MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: A non-randomised, open-label phase 2 study. Lancet Oncol 14:249-256, 2013
    1. 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 19:1315-1327, 2018
    1. 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 119:97-106, 2019
    1. Ascierto PA, Dummer R, Gogas HJ, et al. : Update on tolerability and overall survival in COLUMBUS: Landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. Eur J Cancer 126:33-44, 2020
    1. Gogas H, Dummer R, Ascierto PA, et al. : Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS). Eur J Cancer 152:116-128, 2021
    1. Long GV, Grob JJ, Nathan P, et al. : Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: A pooled analysis of individual patient data from randomised trials. Lancet Oncol 17:1743-1754, 2016
    1. Hauschild A, Larkin J, Ribas A, et al. : Modeled prognostic subgroups for survival and treatment outcomes in BRAF V600-mutated metastatic melanoma: Pooled analysis of 4 randomized clinical trials. JAMA Oncol 4:1382-1388, 2018
    1. Clinical Trials Dashboard: COLUMBUS trial 5-year results.
    1. Ascierto PA, Del Vecchio M, Mackiewicz A, et al. : Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma. J Immunother Cancer 8:e000391, 2020
    1. Ribas A, Daud A, Pavlick AC, et al. : Extended 5-year follow-up results of a phase Ib study (BRIM7) of vemurafenib and cobimetinib in BRAF-mutant melanoma. Clin Cancer Res 26:46-53, 2020
    1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. : Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 381:1535-1546, 2019
    1. Ascierto PA, McArthur GA, Dreno B, et al. : Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): Updated efficacy results from a randomised, double-blind, phase 3 trial. Lancet Oncol 17:1248-1260, 2016
    1. Long GV, Flaherty KT, Stroyakovskiy D, et al. : Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: Long-term survival and safety analysis of a phase 3 study. Ann Oncol 28:1631-1639, 2017
    1. Robert C, Karaszewska B, Schachter J, et al. : Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 372:30-39, 2015
    1. 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 28:1137-1144, 2017
    1. Booth AEC, Hopkins AM, Rowland A, et al. : Risk factors for MEK-associated retinopathy in patients with advanced melanoma treated with combination BRAF and MEK inhibitor therapy. Ther Adv Med Oncol 12:1758835920944359, 2020
    1. Meirson T, Asher N, Bomze D, et al. : Safety of BRAF+MEK inhibitor combinations: Severe adverse event evaluation. Cancers (Basel) 12:1650, 2020
    1. Holbrook K, Lutzky J, Davies MA, et al. : Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series. Cancer 126:523-530, 2020
    1. Fukushima H, Iwata Y, Saito K, et al. : Successful rechallenge therapy for BRAF/MEK inhibitor-resistant multiple brain metastases of melanoma. J Dermatol 48:1291-1295, 2021
    1. Khullar K, Hanft S, Mehnert JM, et al. : Complete response of brainstem metastasis in BRAF-mutated melanoma without stereotactic radiosurgery after initiation of encorafenib and binimetinib. Melanoma Res 31:393-396, 2021
    1. McLoughlin EM, Fadul CE, Patel SH, et al. : Clinical and radiographic response of leptomeningeal and brain metastases to encorafenib and binimetinib in a patient with BRAF V600E-mutated lung adenocarcinoma. J Thorac Oncol 14:e269-e271, 2019

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