Adjuvant Dabrafenib plus Trametinib in Stage III BRAF‐Mutated Melanoma

@article{Long2017AdjuvantDP,
  title={Adjuvant Dabrafenib plus Trametinib in Stage III BRAF‐Mutated Melanoma},
  author={Georgina V. Long and Axel Hauschild and Mario Santinami and Victoria G. Atkinson and Mario Mandal{\`a} and Vanna Chiarion-Sileni and James Larkin and Marta Nyakas and Caroline Dutriaux and Andrew Haydon and Caroline Robert and Laurent Mortier and Jacob Schachter and Dirk Schadendorf and Thierry Lesimple and Ruth Plummer and Ran Ji and Pingkuan Zhang and Bijoyesh Mookerjee and Jeffrey J. Legos and Richard F. Kefford and Reinhard Dummer and John M. Kirkwood},
  journal={The New England Journal of Medicine},
  year={2017},
  volume={377},
  pages={1813–1823}
}
BACKGROUND Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. METHODS In this double‐blind, placebo‐controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF… Expand
The Clinical Efficacy of Dabrafenib Plus TrametinibCombination Treatment in Stage III/IVBRAF-Mutated Melanoma
TLDR
These clinical trials identify combination treatment of dabrafenib plus trametinib as front-line therapy in stage III/IV BRAF-mutated melanoma. Expand
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma
TLDR
As adjuvant therapy for high‐risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence‐free survival than placebo, with no new toxic effects identified. Expand
Adjuvant dabrafenib plus trametinib versus placebo in patients with resected, BRAFV600-mutant, stage III melanoma (COMBI-AD): exploratory biomarker analyses from a randomised, phase 3 trial.
TLDR
Tumour mutational burden alone or in combination with IFNγ gene expression signature or other markers for an adaptive immune response might be of relevance for identifying patients with stage III melanoma who might derive clinical benefit from targeted therapy. Expand
Open-label, phase IIa study of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma.
TLDR
These results support the efficacy and tolerability of dabrafenib in combination with trametinib in East Asian patients with unresectable or metastatic BRAF V600-mutant cutaneous melanoma. Expand
Combined ipilimumab and nivolumab first‐line and after BRAF‐targeted therapy in advanced melanoma
TLDR
While first‐line efficacy appears comparable to trial populations, BRAF‐mutant patients failing prior BRAF/MEK inhibitors show less response, particularly in the setting of serine/threonine‐protein kinase B‐Raf‐targeted therapy. Expand
Patient-reported outcomes in patients with resected, high-risk melanoma with BRAFV600E or BRAFV600K mutations treated with adjuvant dabrafenib plus trametinib (COMBI-AD): a randomised, placebo-controlled, phase 3 trial.
TLDR
The patient-reported outcomes from COMBI-AD are reported, showing that dabrafenib plus trametinib significantly improved relapse-free survival at 3 years and health-related quality of life was similar between groups and did not differ from baseline scores. Expand
Longer Follow-Up Confirms Relapse-Free Survival Benefit With Adjuvant Dabrafenib Plus Trametinib in Patients With Resected BRAF V600–Mutant Stage III Melanoma
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  • Medicine
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2018
TLDR
An updated RFS analysis on the basis of extended study follow-up and a cure-rate model analysis suggested that dabrafenib plus trametinib benefited patients regardless of baseline factors, including disease stage, nodal metastatic burden, and ulceration. Expand
Neoadjuvant dabrafenib combined with trametinib for resectable, stage IIIB-C, BRAFV600 mutation-positive melanoma (NeoCombi): a single-arm, open-label, single-centre, phase 2 trial.
TLDR
Neoadjuvant dabrafenib plus trametinib therapy could be considered in the management of RECIST-measurable resectable stage III melanoma as it led to a high proportion of patients achieving a complete response according to RECIST and a highportion of patients achieved a complete pathological response, with no progression during neoadjuant therapy. Expand
Treatment exceeds expectations with vemurafenib monotherapy in a patient with BRAFV600E-mutant metastatic melanoma
  • M. Yılmaz, Şermin Güven Meşe
  • Medicine
  • Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
  • 2020
TLDR
A case of BRAFV600E-mutant metastatic melanoma, which is being treated with vemurafenib monotherapy with complete response for about seven years, is presented. Expand
Frequent brain metastases during treatment with BRAF/MEK inhibitors: A retrospective single institutional study
TLDR
Frequency of brain metastasis development during treatment with BRAF/MEK inhibitors may be more frequent than anti‐PD‐1 antibody monotherapy, even though the extracranial metastases are well controlled, and frequent brain examinations are recommended to detect BM at an early stage. Expand
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TLDR
The presence of mutant BRAF had no impact on the disease-free interval from diagnosis of first-ever melanoma to first distant metastasis; however, it may have impacted survival thereafter. Expand
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