Clinical and radiological response of BRAF inhibition and MEK inhibition in patients with brain metastases from BRAF-mutated melanoma.

Abstract:

:Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8-15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9-13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6-6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30-0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2-8.5), 5.7 months (95% CI: 3.0-8.4) for dabrafenib, and 3.6 months (95% CI: 3.5-3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT.

journal_name

Melanoma Res

journal_title

Melanoma research

authors

Geukes Foppen MH,Boogerd W,Blank CU,van Thienen JV,Haanen JB,Brandsma D

doi

10.1097/CMR.0000000000000429

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

126-133

issue

2

eissn

0960-8931

issn

1473-5636

journal_volume

28

pub_type

杂志文章
  • BRAF inhibition for advanced locoregional BRAF V600E mutant melanoma: a potential neoadjuvant strategy.

    abstract::Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0000000000000214

    authors: Sloot S,Zager JS,Kudchadkar RR,Messina JL,Benedict JJ,Gonzalez RJ,DeConti R,Turner LM,McCardle T,Smalley KS,Weber JS,Sondak VK,Gibney GT

    更新日期:2016-02-01 00:00:00

  • Parallel risk assessment of melanoma and basal cell carcinoma: skin characteristics and sun exposure.

    abstract::In this study we compared the strength of the association of constitutional factors and sun exposure with cutaneous malignant melanoma (CMM) and basal cell carcinoma (BCC). We analysed 260 incident cases of CMM, 425 incident cases of BCC and two sets of population controls from previous case-control studies conducted ...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199812000-00013

    authors: Rosso S,Zanetti R,Pippione M,Sancho-Garnier H

    更新日期:1998-12-01 00:00:00

  • Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E.

    abstract::BRAF mutations are found in ~50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAF-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutati...

    journal_title:Melanoma research

    pub_type: 杂志文章,多中心研究

    doi:10.1097/CMR.0000000000000398

    authors: Hallmeyer S,Gonzalez R,Lawson DH,Cranmer LD,Linette GP,Puzanov I,Taback B,Cowey CL,Ribas A,Daniels GA,Moore T,Gibney GT,Tawbi H,Whitman E,Lee G,Mun Y,Liu S,Hamid O

    更新日期:2017-12-01 00:00:00

  • Cytotoxic effects of violacein in human uveal melanoma cell lines.

    abstract::Violacein is the main pigment produced by Chromobacterium violaceum, a saprophytic gram-negative bacillus. Violacein is formed by the condensation of two modified tryptophan molecules and has potential anti-neoplastic effects. The purpose of this pilot study was to investigate the in vitro activity of violacein in hum...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200410000-00014

    authors: Saraiva VS,Marshall JC,Cools-Lartigue J,Burnier MN Jr

    更新日期:2004-10-01 00:00:00

  • Biological and enzymatic features of human melanoma clones with different invasive potential.

    abstract::Cell clones derived from a human melanoma metastasis selected for different integrin profiles were examined in vitro for invasive potential and biological and biochemical features potentially related to this process. Clones which expressed high levels of integrins showed high invasive potential, extracellular matrix d...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199212000-00012

    authors: Supino R,Mapelli E,Sanfilippo O,Silvestro L

    更新日期:1992-12-01 00:00:00

  • Prognosis of endoscopic surgery and traditional open resection in mucosal melanoma of the nasal cavity and paranasal sinus.

    abstract::Mucosal melanoma of the nasal cavity and paranasal sinus is always associated with poor prognosis, and 5-year overall survival does not exceed 40%. Our study aimed to compare the intraoperative conditions and prognosis of different surgical techniques to determine the optimum surgical approach for patients with mucosa...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0000000000000516

    authors: Yin G,Guo W,Chen X,Huang Z

    更新日期:2019-02-01 00:00:00

  • Accumulation of p53 protein in human malignant melanoma. Relationship to clinical outcome.

    abstract::Paraffin-embedded tissue from the primary tumours of 116 patients with malignant melanoma, and in 40 cases also from corresponding metastases, were examined for accumulation of p53 protein. The fraction of tumours with positive p53 immunostaining was 13% in the least invasive and 36% in the most invasive primary lesio...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199506000-00007

    authors: Flørenes VA,Holm R,Fodstad O

    更新日期:1995-06-01 00:00:00

  • Expression of angiogenic and immunosuppressive factors by uveal melanoma cell lines.

    abstract::Dissemination of uveal melanomas is almost exclusively haematogenous, making angiogenesis of the tumour a prerequisite for the formation of metastases. Uveal melanomas must employ strategies to evade the immune system in order to escape immune surveillance. We therefore determined the expression of the following angio...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199910000-00003

    authors: Ijland SA,Jager MJ,Heijdra BM,Westphal JR,Peek R

    更新日期:1999-10-01 00:00:00

  • In vitro evaluation of fotemustine as a potential agent for limb perfusion in melanoma.

    abstract::The mechanism of action of fotemustine, a relatively new chloroethylnitrosourea, was evaluated in human melanoma cells in order to assess its potential as an agent for hyperthermic limb perfusion. Fotemustine was more toxic to O6-alkylguanine methyl transferase (AGT) deficient (Mer-) cells than Mer+ cells, implicating...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199802000-00012

    authors: Hayes MT,Bartley J,Parsons PG

    更新日期:1998-02-01 00:00:00

  • Sentinel node localization in primary melanoma: learning curve and results.

    abstract::Ninety primary melanoma patients were studied to investigate the importance of adopting the simultaneous use of patent blue dye (PBD) and lymphoscintigraphy plus gamma detection probe to locate the sentinel node (SN). In total 135 SNs in 105 basins were visualized preoperatively under a gamma camera after lymphoscinti...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199912000-00008

    authors: Testori A,Bartolomei M,Grana C,Mezzetti M,Chinol M,Mazzarol G,Lazzari I,Paganelli G,Geraghty JG,Andreoni B,Veronesi U

    更新日期:1999-12-01 00:00:00

  • Responses to ultraviolet-B in cell lines from hereditary melanoma kindreds.

    abstract::Ultraviolet-B (UV-B) triggers a cascade of events involving cell cycle control genes leading ultimately to DNA repair or apoptosis. The hypothesis examined here is that the genetic abnormality predisposing to melanoma affects the ability of the cell to respond appropriately to UV-B, so favouring mutagenesis. Epstein-B...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200102000-00001

    authors: Shannon JA,Kefford RF,Mann GJ

    更新日期:2001-02-01 00:00:00

  • Immune-related Bell's palsy in melanoma patients treated with immune checkpoint inhibitors.

    abstract::Immune-checkpoint inhibitors (ICIs) exposed the oncology community to novel immune-related adverse events (irAEs). Here, we report on a retrospective analysis of patients with melanoma who developed an ICI-related, unilateral, acute and peripheral facial nerve paralysis (Bell's palsy).We retrospectively reviewed all t...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0000000000000715

    authors: Beninato T,Fucà G,Di Guardo L,Vetrano I,Valeri B,Nesa F,Del Vecchio M,Cimminiello C

    更新日期:2021-01-22 00:00:00

  • A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes.

    abstract::The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition i...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0000000000000174

    authors: Sarojini S,Pecora A,Milinovikj N,Barbiere J,Gupta S,Hussain ZM,Tuna M,Jiang J,Adrianzen L,Jun J,Catello L,Sanchez D,Agarwal N,Jeong S,Jin Y,Remache Y,Goy A,Ndlovu A,Ingenito A,Suh KS

    更新日期:2015-10-01 00:00:00

  • Effect of pEgr-TNFalpha gene radiotherapy on mice melanoma.

    abstract::In the present study, we constructed a pEgr-tumour necrosis factor-alpha (TNFalpha) plasmid and investigated its expression properties in B16 cells on exposure to ionizing irradiation and, furthermore, the effect of gene radiotherapy on a melanoma model. Firstly, the recombinant pEgr-TNFalpha plasmid was constructed a...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200506000-00007

    authors: Wu C,Li X,Tian M

    更新日期:2005-06-01 00:00:00

  • In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunity.

    abstract::When cancer cells, including melanoma cells, are genetically altered to secrete cytokines, irradiated and injected into subjects, long-term antitumour immunity is induced. Optimally, existing melanomas induced to produce cytokines in vivo could stimulate this same immune response. Although in vivo electroporation enha...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200012000-00010

    authors: Heller L,Pottinger C,Jaroszeski MJ,Gilbert R,Heller R

    更新日期:2000-12-01 00:00:00

  • The polymerization of melanin: a poorly understood phenomenon with egregious biological implications.

    abstract::Several hypotheses have explicitly implicated the role of an altered redox status of melanin in the aetiology of melanoma and macular degeneration. The balance between the intrinsic anti-oxidant and pro-oxidant properties of melanin is lost, resulting in an altered redox phenotype. We propose that such an alteration o...

    journal_title:Melanoma research

    pub_type: 杂志文章,评审

    doi:10.1097/01.cmr.0000195699.35143.df

    authors: Sarangarajan R,Apte SP

    更新日期:2006-02-01 00:00:00

  • Clinical significance of serum M30 and M65 levels in melanoma.

    abstract::M30 and M65 are relatively new assays that detect different circulating forms of the epithelial cell structural protein cytokeratin 18. This study was carried out to investigate the serum levels of M30 and M65 in patients with melanoma and the relationship with tumor progression and known prognostic parameters. Fifty-...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0b013e328363e4ab

    authors: Tas F,Karabulut S,Serilmez M,Yildiz I,Sen F,Ciftci R,Duranyildiz D

    更新日期:2013-10-01 00:00:00

  • Analysis of candidate genes through a proteomics-based approach in primary cell lines from malignant melanomas and their metastases.

    abstract::Proteomics provides a powerful approach for screening alterations in protein expression and post-translational modification associated with particular human diseases. In this study, the analysis of protein expression was focused on malignant melanoma in order to determine the candidate genes involved in tumour progres...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200508000-00002

    authors: Carta F,Demuro PP,Zanini C,Santona A,Castiglia D,D'Atri S,Ascierto PA,Napolitano M,Cossu A,Tadolini B,Turrini F,Manca A,Sini MC,Palmieri G,Rozzo AC,Italian Melanoma Intergroup.

    更新日期:2005-08-01 00:00:00

  • Compliance with guidelines in the surgical management of cutaneous melanoma across the USA.

    abstract::The National Comprehensive Cancer Network has formulated guidelines for the management of cutaneous malignant melanoma with regard to resection margins (RMs) and regional staging. The aim of this study was to assess compliance with these recommendations in the general population of the USA. The Surveillance, Epidemiol...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0b013e32836254bd

    authors: Wasif N,Gray RJ,Bagaria SP,Pockaj BA

    更新日期:2013-08-01 00:00:00

  • Expression of Bcl-2 family members in human melanocytes, in melanoma metastases and in melanoma cell lines.

    abstract::In human melanoma no complete information about the expression of the apoptosis-promoting and apoptosis-inhibiting members of the Bcl-2 family has been available to date. In this study we have investigated by Western blotting the expression pattern of Bcl-2 and its homologues Bax, Bak, Bcl-xL, Bcl-xS, Mcl-1 and Bad in...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199806000-00001

    authors: Selzer E,Schlagbauer-Wadl H,Okamoto I,Pehamberger H,Pötter R,Jansen B

    更新日期:1998-06-01 00:00:00

  • Lovastatin-induced apoptosis in human melanoma cell lines.

    abstract::The cholesterol-lowering medications, statins, inhibit cellular proliferation and induce apoptosis in an array of cancer cell lines, including melanoma. We investigated the apoptotic mechanism of lovastatin on human melanoma cell lines in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell T...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200504000-00001

    authors: Shellman YG,Ribble D,Miller L,Gendall J,Vanbuskirk K,Kelly D,Norris DA,Dellavalle RP

    更新日期:2005-04-01 00:00:00

  • Association between germ cell tumours, large numbers of naevi, atypical naevi and melanoma.

    abstract::Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed up after treatment of germ cell tumours (GCTs) who were referred to the dermatologist for multiple ...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200104000-00005

    authors: Avril MF,Chompret A,Verne-Fourment L,Terrier-Lacombe MJ,Spatz A,Fizazi K,Bressac-de Paillerets B,Demenais F,Théodore C

    更新日期:2001-04-01 00:00:00

  • The effect of delay time between primary melanoma biopsy and sentinel lymph node dissection on sentinel node status, recurrence, and survival.

    abstract::For primary melanoma, there is a delay between the initial skin biopsy and sentinel lymph node dissection, which may cause anxiety for the patient. The consequences of this delay on disease progression are unknown. The goal of this study was to determine whether delay time for sentinel node dissection from the initial...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0b013e32835861f6

    authors: Parrett BM,Accortt NA,Li R,Dosanjh AS,Thummala S,Kullar R,Cleaver JE,Kashani-Sabet M,Leong SP

    更新日期:2012-10-01 00:00:00

  • Dermatomyositis in a patient undergoing nivolumab therapy for metastatic melanoma: a case report and review of the literature.

    abstract::Checkpoint inhibitor immunotherapy is a transformative treatment for advanced malignancies, but can be associated with numerous immune-related adverse events (irAEs). The majority of irAEs include those that closely resemble known cutaneous and neurocutaneous autoimmune or autoinflammatory diseases, such as scleroderm...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0000000000000642

    authors: Kosche C,Stout M,Sosman J,Lukas RV,Choi JN

    更新日期:2020-06-01 00:00:00

  • Coordinated mRNA expression of c-Kit with tyrosinase and TRP-1 in melanin pigmentation of normal and malignant human melanocytes and transient activation of tyrosinase by Kit/SCF-R.

    abstract::The proto-oncogene c-Kit encodes a membrane receptor protein with intrinsic tyrosine kinase activity. Activation of c-Kit induces cell proliferation, differentiation or migration among different cell types. The present study provides evidence that c-Kit plays an important role in the cell differentiation rather than i...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199510000-00002

    authors: Luo D,Chen H,Searles G,Jimbow K

    更新日期:1995-10-01 00:00:00

  • Phase I-II trial of hyperthermic isolated limb perfusion with cisplatin in the treatment of high risk malignant melanoma of the extremities.

    abstract::Between 1983 and 1990, 59 patients with malignant melanoma were retrospectively reviewed to assess the safety, efficacy and the maximal tolerated dose of cisplatin used in hyperthermic isolated limb perfusion. The median follow-up was 29 months (range 3-54 months). The local recurrence rate was 12% in Stage I, 33% in ...

    journal_title:Melanoma research

    pub_type: 临床试验,杂志文章

    doi:10.1097/00008390-199104000-00007

    authors: Hajarizadeh H,Mueller CR,Woltering EA,Small K,Fletcher WS

    更新日期:1991-04-01 00:00:00

  • Melanoma vasculogenic mimicry is strongly related to reactive oxygen species level.

    abstract::The concept of 'vasculogenic mimicry' (VM) was introduced to describe the unique ability of highly invasive tumor cells to form capillary-like structures (CLS) and matrix-rich patterned network in three-dimensional culture that mimic embryonic vasculogenic network. Recently, we have shown that CLS formation requires a...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0b013e3282f1d2ec

    authors: Vartanian AA,Burova OS,Stepanova EV,Baryshnikov AY,Lichinitser MR

    更新日期:2007-12-01 00:00:00

  • A purified GM3 ganglioside conjugated vaccine induces specific, adjuvant-dependent and non-transient antitumour activity against B16 mouse melanoma in vitro and in vivo.

    abstract::The presence of substantial amounts of GM3 ganglioside on human melanomas and other tumours, together with its peculiar biological properties, makes this glycolipid a unique target for cancer immunotherapy. B16 mouse melanoma expresses GM3 and constitutes an appropriate model for the development of novel GM3-based vac...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-200106000-00003

    authors: Carr A,Mazorra Z,Alonso DF,Mesa C,Valiente O,Gomez DE,Perez R,Fernandez LE

    更新日期:2001-06-01 00:00:00

  • Validation of dabrafenib-trametinib prognostic groups in patients treated with vemurafenib and cobimetinib for advanced BRAF-mutated melanoma.

    abstract::Prognostic groups defined by lactate dehydrogenase concentration and number of organ sites containing metastases have been reported for patients treated with dabrafenib and trametinib for advanced melanoma. We aimed to validate these prognostic groups for patients treated with vemurafenib and cobimetinib in the coBRIM...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/CMR.0000000000000634

    authors: Sorich MJ,Rowland A,Hopkins AM

    更新日期:2020-06-01 00:00:00

  • Limitations of high frequency ultrasound in determining the invasiveness of cutaneous malignant melanoma.

    abstract::Preoperative assessment of melanoma invasion by sonometry has been reported to exhibit a high correlation with postoperative histometry based on the determination of a regression coefficient. We believe that this approach is not adequate and that it can be misleading. We therefore applied an appropriate statistical ap...

    journal_title:Melanoma research

    pub_type: 杂志文章

    doi:10.1097/00008390-199610000-00007

    authors: Partsch B,Binder M,Püspök-Schwarz M,Wolff K,Pehamberger H

    更新日期:1996-10-01 00:00:00