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Variants & evidence
413 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| BRAF V600G1 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | C | Does Not Support Sensitivity Response | 3 | submitted | EID7618In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF V600K28 | ||||||||
| (oncogenic) | Melanoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13233Deichmann et al. analyzed BRAF exon 15 in 60 cutaneous/subcutaneous melanoma metastases from 60 patients using PCR-SSCP followed by cloning and sequencing. BRAF V599K (current nomenclature V600K) was … (full text at CIViC) PMID 15935100 · Deichmann et al., 2005 · Open in CIViC | civic |
| 〃 | Melanoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13235Ponti et al. described seven patients with BRAF V600K-mutated melanoma, including six men and one woman aged 48–82 years. Four of seven primary melanomas arose on the scalp. Dermoscopic images availab… (full text at CIViC) PMID 25323827 · Ponti et al., 2015 · Open in CIViC | civic |
| 〃 | Melanoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | ||
| BRAF V600_K601DELINSD2 | ||||||||
| Vemurafenib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | — | submitted | EID4789In a stage IV cutaneous nodular thoracic melanoma patient with pulmonary, liver and brain metastases, harboring a BRAF V600_K601delinsD mutation, stable disease to vemurafenib monotherapy was reported… (full text at CIViC) PMID 25265970 · Trudel et al., 2014 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | C | Supports Sensitivity Response | — | submitted | EID4790In a stage IIIc melanoma patient harboring BRAF V600_K601delinsD mutation, response to vemurafenib monotherapy was reported. The patient achieved a reduction in the size of axillary and pectoral subcu… (full text at CIViC) PMID 24108467 · Busser et al., 2013 · Open in CIViC | civic |
| BRAF V600_K601>E2 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID7617In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination | Melanoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7630In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF V600K + PREX2 R172IBRAFPREX21 | ||||||||
| Vemurafenib | Melanoma | Predictive | C | Supports Resistance | 2 | accepted | EID6268In a retrospective study of 44 relapsed melanoma patients harboring BRAF V600E/K (known BRAF inhibitor sensitizing mutations), PREX2 R172I was associated with a case of acquired resistance to BRAF inh… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC | civic |
| BRAF V600L1 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | C | Does Not Support Sensitivity Response | 3 | submitted | EID7619In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF V600M1 | ||||||||
| BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7631In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF V600R7 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID7615In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID7628In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| Dabrafenib | Melanoma | Predictive | C | |||||
| BRAF Non-V600 + BRAF V600R1 | ||||||||
| Dabrafenib + TrametinibCombination | Melanoma | Predictive | B | Supports Sensitivity Response | 1 | submitted | EID11308In this phase 1/2, open-label study 247 patients with metastatic melanoma and BRAF V600 mutations V600 (only one patient with a non-V600E/V600K with a BRAF V600R) were enrolled. Part 1 evaluated the p… (full text at CIViC) PMID 23020132 · Flaherty et al., 2012 · Open in CIViC | civic |
| BRAF V600_S602>DT1 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | C | Does Not Support Sensitivity Response | 3 | submitted | EID7620In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF V601E2 | ||||||||
| BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7633In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| Mitogen-Activated Protein Kinase Kinase Inhibitor | Melanoma | Predictive | C | Does Not Support Sensitivity Response | 3 | submitted | EID7627In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC | civic |
| BRAF Wildtype1 | ||||||||
| MEK Inhibitor RO4987655 | Melanoma | Predictive | B | Does Not Support Resistance | 2 | accepted | EID995Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655. Among 12 patients with melanoma BRAF wild type and non-NRAS or NRAS unknown status, seven patients experienced partial … (full text at CIViC) PMID 24947927 · Zimmer et al., 2014 · Open in CIViC | civic |
| BRD4 Overexpression1 | ||||||||
| Unspecified therapy | Melanoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID9315BET inhibitor JQ-1 induced a decrease in viability to NRAS mutant melanoma cells with an increase in sensitivity in those highly expressing BRD4 in comparison to BRD2 and BRD3 expression (P = 0.018); … (full text at CIViC) PMID 29650805 · Echevarría-Vargas et al., 2018 · Open in CIViC | civic |
| CCND1 Amplification1 | ||||||||
| Carboplatin + Paclitaxel + SorafenibCombination | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID1495Retrospective analysis of somatic mutations and copy number changes in 119 patient treated with carboplatin, paclitaxel, ± sorafenib (CPS) in the E2603 trial. CPS therapy was associated with improved … (full text at CIViC) PMID 26307133 · Wilson et al., 2016 · Open in CIViC | civic |
Data updated 1 hour agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
Lyle et al. assessed clinically significant somatic mutations in a cohort of Australian patients with unresectable stage IIIC or stage IV melanoma. BRAF V600 mutation testing was performed in 713 pati… (full text at CIViC)
PMID 27020391 · Lyle et al., 2016 · Open in CIViC
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| 〃 | Melanoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13237Sanna et al. performed ultra-deep targeted sequencing of 40 melanoma-associated genes in 72 primary cutaneous melanomas. BRAF mutations were detected in 35/72 (49%) tumors, including BRAF V600K in 7/3… (full text at CIViC) PMID 31811783 · Sanna et al., 2020 · Open in CIViC | civic |
| 〃 | Melanoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13238Pires da Silva et al. molecularly characterized BRAF V600K-mutant melanoma using pretreatment tumors from 15 patients with metastatic melanoma and an independent TCGA cohort containing 17 V600K tumors… (full text at CIViC) PMID 30630828 · Pires da Silva et al., 2019 · Open in CIViC | civic |
| 〃 | Melanoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13239Lokhandwala et al. performed targeted next-generation sequencing of 446 melanomas in a clinical diagnostic setting. BRAF mutations were detected in 189/446 (42%) tumors, including BRAF V600K in 27/446… (full text at CIViC) PMID 31277584 · Lokhandwala et al., 2019 · Open in CIViC | civic |
| 〃 | Melanoma | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13240Menzies et al. prospectively evaluated 308 patients with unresectable stage IIIC or stage IV melanoma and identified BRAF mutations in 143 (46%), including BRAF V600K in 27/143 (19%) BRAF-mutant patie… (full text at CIViC) PMID 22535154 · Menzies et al., 2012 · Open in CIViC | civic |
| 〃 | Melanoma | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID13234Pollock et al. analyzed BRAF exon 15 in melanocytic lesions and identified a tandem GT→AA mutation resulting in BRAF V599K (current nomenclature V600K) in two melanoma metastases. The V599K alteration… (full text at CIViC) PMID 12447372 · Pollock et al., 2003 · Open in CIViC | civic |
| Dabrafenib | Melanoma | Predictive | B | Supports Sensitivity Response | — | accepted | EID2505Patients were treated with a specific RAF inhibitor (dabrafenib), which improved overall survival of patients with BRAF mutations (P<0.003), compared to non-treated patients with BRAF mutations. Patie… (full text at CIViC) PMID 21343559 · Long et al., 2011 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | — | submitted | EID2507Proposed resistance mechanisms include PDGFRB upregulation or NRAS mutations resulting in MAPK pathway reactivation, but not secondary mutations in BRAF. MEK inhibitors may demonstrate clinical benefi… (full text at CIViC) PMID 21107323 · Nazarian et al., 2010 · Open in CIViC | civic |
| Dabrafenib + TrametinibCombination | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID6179Adjuvant dual treatment with BRAF inhibitor dabrafenib and MEK inhibitor trametinib was administered to patients with stage III resected melenoma with V600E or V600K mutation in this stage III trial (… (full text at CIViC) PMID 28891408 · Long et al., 2017 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID6941In this Phase I and II study (NCT01072175), patients with metastatic melanoma were treated with either a combination of dabrafenib and trametinib or dabrafenib monotherapy. Among patients with the V60… (full text at CIViC) PMID 23020132 · Flaherty et al., 2012 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID6965In this Phase III trial (coBRIM, NCT01689519) of 495 V600 mutant melanoma patients, 56 had V600K mutation. 32 patients were treated with vemurafenib and placebo, and 24 were treated with vemurafenib a… (full text at CIViC) PMID 25265494 · Larkin et al., 2014 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID6939In this Phase III trial (NCT01584648 COMBI-d), previously untreated patients with unrescectable stage IIIC or IV melanoma with BRAF V600E (359 patients) or V600K (61 patients) received dabrafenib and … (full text at CIViC) PMID 25265492 · Long et al., 2014 · Open in CIViC | civic |
| Binimetinib + EncorafenibCombination | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID13183In the randomized phase III COLUMBUS trial of patients with locally advanced unresectable or metastatic BRAF V600-mutant melanoma, 22 patients with BRAF V600K received encorafenib plus binimetinib and… (full text at CIViC) PMID 29573941 · Dummer et al., 2018 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13185In the 5-year update of the randomized phase III COLUMBUS trial of patients with locally advanced unresectable or metastatic BRAF V600-mutant melanoma, 22 patients with BRAF V600K received encorafenib… (full text at CIViC) PMID 35862871 · Dummer et al., 2022 · Open in CIViC | civic |
| Trametinib | Melanoma | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID2506In a study of 322 advanced melanoma patients with BRAF-V600E (N=281), BRAF-V600K (N=40), or both mutations (N=1), treatment with trametinib was associated with improved progression-free survival (4.8m… (full text at CIViC) PMID 22663011 · Flaherty et al., 2012 · Open in CIViC | civic |
| Dabrafenib + TrametinibCombination | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4181In a phase 3 clinical trial (NCT01597908) involving 704 patients with metastatic melanoma harboring BRAF V600 mutations, a subgroup analysis of patients with V600K mutations showed an objective respon… (full text at CIViC) PMID 25399551 · Robert et al., 2015 · Open in CIViC | civic |
| Vemurafenib | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1399In the Phase III study of vemurafenib versus dacarbazine BRIM-3 (NCT01006980) in metastatic melanoma, 57 patients were confirmed to have V600K mutation. In this subgroup of treatment-naive patients, s… (full text at CIViC) PMID 24508103 · McArthur et al., 2014 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID4177In the phase II BRIM-2 trial (NCT00949702), 132 patients with BRAF V600-mutant metastatic melanoma received vemurafenib monotherapy. The overall RECIST v1.1 objective response rate was 53% (70/132), i… (full text at CIViC) PMID 23569304 · Trunzer et al., 2013 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4180In a retrospective study of 300 stage IV melanoma patients, patients with BRAF V600K mutation (n=18) were associated with a 5.6% (1/18) complete response, a 22.2% (4/18) partial response and stable di… (full text at CIViC) PMID 25524477 · Ugurel et al., 2015 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 2 | submitted | EID4175In a phase 2 clinical trial (NCT00949702) of 344 BRAF V600 mutation, positive advanced melanoma patients, patients with BRAF V600K (n=10) mutation treated with vemurafenib monotherapy were associated … (full text at CIViC) PMID 22356324 · Sosman et al., 2012 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1400A 53 year old male presented with a scalp lesion which was incompletely excised. Metastases were seen in lymph node biopsy and subsequently in CT. BRAF inhibitor vemurafenib was then administered at 9… (full text at CIViC) PMID 26989536 · Sahadudheen et al., 2016 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID4174A patient with locally advanced unresectable BRAF V600K-mutant melanoma who had previously received topical imiquimod and systemic temozolomide achieved a marked clinical response with substantial tum… (full text at CIViC) PMID 20630094 · Rubinstein et al., 2010 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID4176In a study of 30 patients with BRAF V600-mutant metastatic melanoma treated with BRAF inhibitors, one patient with BRAF V600K melanoma treated with vemurafenib achieved a partial response by RECIST, w… (full text at CIViC) PMID 24463458 · Rizos et al., 2014 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID4179A patient with BRAF V600K melanoma and multiple cerebral metastases was treated with vemurafenib (960 mg twice daily); after 10 weeks, brain MRI demonstrated a reduction in the size and number of cere… (full text at CIViC) PMID 23677116 · Forschner et al., 2013 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4173In vitro, BRAF V600K-mutant melanoma cell cultures were sensitive to vemurafenib (PLX4032), with BRAF-mutant melanoma cultures showing IC50 values of 60–450 nM compared with ≥2.4 uM in BRAF wild-type … (full text at CIViC) PMID 20149136 · Halaban et al., 2010 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID4178In vitro, BRAF V600K-mutant Hmel-1 melanoma cells were more sensitive to vemurafenib than BRAF wild-type LND-1 cells, with IC50 values of 5.5 +/- 0.4 uM and 32.2 +/- 1.1 uM, respectively. PMID 26070258 · Porcelli et al., 2015 · Open in CIViC | civic |
| Does Not Support Resistance |
| 3 |
| submitted |
EID8949A 74 year old male patient was diagnosed with metastatic melanoma following histological assessment of multiple brain and lung tumors. One tumor harbored BRAF V600E and the patient began dabrafenib mo… (full text at CIViC) PMID 23237741 · Klein et al., 2013 · Open in CIViC |
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| Vemurafenib | Melanoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID4170In a retrospective study of 30 metastatic melanoma patients with progressing metastases, a metastatic melanoma patient harboring BRAF V600R mutation achieved a favorable response to vemurafenib treatm… (full text at CIViC) PMID 24463458 · Rizos et al., 2014 · Open in CIViC | civic |
| 〃 | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID4172An 81 year old male was diagnosed with ulcerated cutaneous melanoma of the occiput (M1c), and had undergone several local resections and radiotherapy. A metastasis was found to harbor BRAF V600R mutat… (full text at CIViC) PMID 23237741 · Klein et al., 2013 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID4171In an in vitro study, the WM1341D cell line expressing BRAF V600R was associated with increased sensitivity to vemurafenib treatment, as compared to cell lines expressing BRAF wild-type. Sensitivity w… (full text at CIViC) PMID 20551065 · Yang et al., 2010 · Open in CIViC | civic |
| Dabrafenib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | B | Does Not Support Resistance | 2 | submitted | EID8948Nine patients with BRAF V600R mutated metastatic melanoma were given dabrafenib (n=7) or vemurafenib (n=2) monotherapy as part of a compassionate access program. Five out of six radiographically asses… (full text at CIViC) PMID 23237741 · Klein et al., 2013 · Open in CIViC | civic |