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| BRAF Amplification AND ( BRAF V600E OR BRAF V600K ) | Dabrafenib + VemurafenibSubstitutes | Predictive | B | Supports Resistance | 2 | accepted | EID6262In a retrospective study of 44 relapsed melanoma patients harboring BRAF V600E or V600K (known BRAF inhibitor sensitizing mutations), MAPK pathway reactivation mechanisms were implicated in acquired r… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC | civic |
| BRAF V600E OR BRAF V600K | Dabrafenib + TrametinibCombination | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID93This was a Phase I and II study (NCT01072175) of dabrafenib and trametinib combination therapy vs. dabrafenib monotherapy in patients with metastatic melanoma.
Cutaneous squamous-cell carcinoma was… (full text at CIViC) PMID 23020132 · Flaherty et al., 2012 · Open in CIViC | civic |
| BRAF V600E OR BRAF V600K | Vemurafenib | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1410Phase 2 trial in 132 patients with previously treated metastatic melanoma with BRAF V600E (n=122) or V600K (n=10) mutation.
Confirmed overall response rate was 53% (95% confidence interval [CI], 44 t… (full text at CIViC) PMID 22356324 · Sosman et al., 2012 · Open in CIViC | civic |
| BRAF V600K | (oncogenic) | 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 |
| BRAF V600K | (oncogenic) | 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 |
| BRAF V600K | (oncogenic) | Oncogenic | B | Supports Oncogenicity | 3 | submitted | EID13236Lyle 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 | civic |
| BRAF V600K | (oncogenic) | 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 |
| BRAF V600K | (oncogenic) | 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 |
| BRAF V600K | (oncogenic) | 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 |
| BRAF V600K | (oncogenic) | 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 |
| BRAF V600K | (oncogenic) | 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 |
| BRAF V600K | Dabrafenib | 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 |
| BRAF V600K | Dabrafenib | 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 |
| BRAF V600K | Dabrafenib + TrametinibCombination | 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 |
| BRAF V600K | Dabrafenib + TrametinibCombination | 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 |
| BRAF V600K | Dabrafenib + TrametinibCombination | 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 |
| BRAF V600K | Dabrafenib + TrametinibCombination | 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 |
| BRAF V600K | Binimetinib + EncorafenibCombination | 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 |
| BRAF V600K | Trametinib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K | Vemurafenib | 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 |
| BRAF V600K AND PREX2 R172I | Vemurafenib | 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 |