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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 L5972 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7626In 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 | 3 | submitted | EID7632In 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 L597Q2 | ||||||||
| Trametinib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID4905Case study report including one patient with L597Q mutation-positive metastatic melanoma (M1b disease) treated with the MEK inhibitor trametinib. The L597Q patient achieved a RECIST partial response a… (full text at CIViC) PMID 24933606 · Bowyer et al., 2014 · Open in CIViC | civic |
| Trametinib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1461Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| BRAF L597R2 | ||||||||
| Vemurafenib | Melanoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID728A case report of a patient with BRAF L597R mutation and clinical response to BRAF-inhibition (Vemurafenib) that correlated to in-vitro models. PMID 23715574 · Bahadoran et al., 2013 · Open in CIViC | civic |
| Trametinib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1458Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| BRAF L597S2 | ||||||||
| MEK Inhibitor REC-4881 | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1460Case report of a 69 year old patient with metastatic melanoma treated with MEK inhibitor TAK-733 in a clinical trial. A partial radiographic response with a decrease of 31% in the sum of maximum diame… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| Trametinib + VemurafenibSubstitutes | Cutaneous MelanomaALIAS | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID1459Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC | civic |
| BRAF L597V1 | ||||||||
| Trametinib | Cutaneous MelanomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1463Case report of a phase 1 study in advanced melanoma patients. 97 patients with melanoma were enrolled and treated with trametinib. One patient with a BRAF Leu597Val had a confirmed partial response wi… (full text at CIViC) PMID 22805292 · Falchook et al., 2012 · Open in CIViC | civic |
| BRAF Overexpression1 | ||||||||
| Dabrafenib + PLX4720 + Trametinib + VemurafenibCombination | Melanoma | Predictive | D | Supports Resistance | 2 | submitted | EID10156Association between BRAF-V600E allele amplification and resistance to MEK and BRAF inhibitors was demonstrated in melanoma cell lines and PDX models. Trametinib resistant cells lines distinctly displa… (full text at CIViC) PMID 24055054 · Villanueva et al., 2013 · Open in CIViC | civic |
| BRAF p61BRAF(V600E)2 | ||||||||
| Vemurafenib | Melanoma | Predictive | C | Supports Resistance | 2 | submitted | EID9703A 62 year old male with melanoma was treated with vemurafenib and achieved PFS of 148 days and 47% tumor reduction. Upon progression tumor samples were assessed for mutations in BRAF and NRAS by PCR. … (full text at CIViC) PMID 22113612 · Poulikakos et al., 2011 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Resistance | 4 | submitted | EID9702In an in vitro study, SKMEL-239 cells were exposed to 2uM vemurafenib for 2 months. Five independent cell lines were recovered and assessed for resistance alterations. Three cell lines expressing p61B… (full text at CIViC) PMID 22113612 · Poulikakos et al., 2011 · Open in CIViC | civic |
| BRAF T599_V600insT1 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | C | Does Not Support Sensitivity Response | 3 | submitted | EID7625In 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 V60017 | ||||||||
| (diagnostic) | Melanoma | Diagnostic | B | Supports Positive | 4 | accepted | EID30BRAF mutations are associated with melanoma arising in non-chronic sun damaged skin and with superficial spreading melanoma. PMID 21166657 · Lee et al., 2011 · Open in CIViC | civic |
| Atezolizumab + Cobimetinib + VemurafenibCombination | Melanoma | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID11238In this phase 3, randomised, double-blind, placebo-controlled trial, 514 patients with unresectable stage IIIc–IV, BRAFV600 mutation-positive melanoma were randomly assigned to either 28-day cycles of… (full text at CIViC) PMID 32534646 · Gutzmer et al., 2020 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | A | Supports Sensitivity Response | 4 | |||
| BRAF Amplification + BRAF V6001 | ||||||||
| Dabrafenib + TrametinibCombination | Melanoma | Predictive | C | Supports Resistance | 4 | accepted | EID7677In a retrospective study, authors analyzed BRAF V600 mutated melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and geneti… (full text at CIViC) PMID 25452114 · Long et al., 2014 · Open in CIViC | civic |
| BRAF V600 + PTEN UnderexpressionBRAFPTEN1 | ||||||||
| Vemurafenib | Melanoma | Predictive | D | Supports Resistance | 4 | accepted | EID6271An in vitro study of M229 (a human melanoma cell line) endogenously expressing wildtype PTEN and BRAF V600E (a known BRAF inhibitor sensitizing mutation) found that PTEN knockdown cells (achieved via … (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC | civic |
| BRAF V600D5 | ||||||||
| BRAF Inhibitor | Melanoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID7616In 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 | EID7629In 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 | B | |||||
| BRAF V600E13 | ||||||||
| (prognostic) | Melanoma | Prognostic | B | Supports Poor Outcome | 3 | accepted | EID104BRAF V600E is correlated with shorter disease-free and overall Survival in a Spanish cohort of melanoma patients. PMID 24388723 · Nagore et al., 2014 · Open in CIViC | civic |
| 〃 | Melanoma | Prognostic | B | Does Not Support Poor Outcome | 2 | accepted | EID82BRAF status does not predict outcome in patients treated with dacarbazine or temozolomide. PMID 24586605 · Meckbach et al., 2014 · Open in CIViC | civic |
| (oncogenic) | Melanoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID13053In this study, BRAF V600E, reported as V599E, was identified as a recurrent somatic variant in melanoma. When transiently expressed in COS cells, BRAF V600E demonstrated approximately 10.7-fold greate… (full text at CIViC) | |
Data updated 11 hours 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.
EID13046In the second interim analysis of the randomized phase III IMspire150 trial (NCT02908672), 514 patients with previously untreated unresectable stage IIIc or stage IV BRAF V600 mutation-positive melano… (full text at CIViC) PMID 36460017 · Ascierto et al., 2023 · Open in CIViC |
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| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13043In a multicenter, open-label phase Ib dose-escalation and cohort-expansion study (NCT01656642), 39 checkpoint inhibitor-naive patients with previously untreated, unresectable stage IIIC or metastatic … (full text at CIViC) PMID 31171876 · Sullivan et al., 2019 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13044In the multicenter, open-label, single-arm phase II TRICOTEL study (NCT03625141), 65 patients with previously untreated BRAF V600 mutation-positive metastatic melanoma and CNS metastases received vemu… (full text at CIViC) PMID 37459873 · Dummer et al., 2023 · Open in CIViC | civic |
| Cobimetinib + VemurafenibCombination | Melanoma | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID6044In this double-blind, randomized, placebo-controlled, multicentre study, adult patients with histologically confirmed BRAF(V600) mutation-positive unresectable stage IIIC or stage IV melanoma were ran… (full text at CIViC) PMID 27480103 · Ascierto et al., 2016 · Open in CIViC | civic |
| Dabrafenib | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1407In the NCT00880321 trial using mutant BRAF inhibitor dabrafenib in solid tumors, 10 cases of melanoma brain metastases were assessed for dabrafenib response. In nine patients a decrease in size of met… (full text at CIViC) PMID 22608338 · Falchook et al., 2012 · Open in CIViC | civic |
| Dabrafenib + TrametinibCombination | Melanoma | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID6937In this Phase III trial (NCT01584648 COMBI-d), 423 previously untreated patients with unresectable stage IIIC or IV BRAF V600E or V600K mutant melanoma received dabrafenib and trametinib or dabrafenib… (full text at CIViC) PMID 25265492 · Long et al., 2014 · Open in CIViC | civic |
| Binimetinib + EncorafenibCombination | Melanoma | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7287In a phase 3 trial, patients with melanoma with BRAF V600E or V600K mutation were randomly assigned to encorafenib plus binimetinib or vemurafenib or encorafenib. mPFS was 14·9 months (95% CI 11·0-18·… (full text at CIViC) PMID 29573941 · Dummer et al., 2018 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID13042In the multicenter, open-label phase Ib/II trial NCT01543698, 55 patients with BRAF V600-mutant metastatic melanoma who had not previously received a BRAF inhibitor were treated with encorafenib plus … (full text at CIViC) PMID 32669376 · Sullivan et al., 2020 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID13184In a multicenter, open-label phase Ib/II study, 55 BRAFi-naïve patients with BRAF-mutant melanoma, including 49 (89%) with BRAF V600E and 5 (9%) with BRAF V600K, received encorafenib plus binimetinib.… (full text at CIViC) PMID 32669376 · Sullivan et al., 2020 · Open in CIViC | civic |
| Refametinib | Melanoma | Predictive | C | Supports Resistance | 2 | accepted | EID1000Phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766. 2 of 2 patients with BRAF mutant melanoma had moderate progressive disease (despite receiving the highest doses adminis… (full text at CIViC) PMID 23434733 · Weekes et al., 2013 · Open in CIViC | civic |
| Trametinib | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1750Patients who had histologically confirmed, unresectable stage IIIC or IV cutaneous melanoma with a V600E or V600K BRAF mutation were eligible for the study. 322 eligible patients (281 with the V600E m… (full text at CIViC) PMID 22663011 · Flaherty et al., 2012 · Open in CIViC | civic |
| Dabrafenib + TrametinibCombination | Cutaneous MelanomaALIAS | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1411The Combi-v (NCT01597908) open-label, randomized phase 3 trial had 704 patients with metastatic melanoma with a BRAF V600 mutation. Patients were randomized to receive either a combination of dabrafen… (full text at CIViC) PMID 25399551 · Robert et al., 2015 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID6180Combination Dabrafenib and Trametinib treatment was assessed for adjuvant treatment of stage III resected BRAF V600 mutant melanoma in the COMBI-AD trial NCT01682083. Patients were treated with combin… (full text at CIViC) PMID 28891408 · Long et al., 2017 · Open in CIViC | civic |
| Cobimetinib + VemurafenibCombination | Melanoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1422In a randomized phase 3 study, previously untreated advanced or metastatic BRAF V600 mutation-positive melanoma patients treated with combination vemurafenib and cobimetinib showed improved progressio… (full text at CIViC) PMID 25265494 · Larkin et al., 2014 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID6966In this Phase 1b study, 129 patients with unresectable or metastatic melanoma were verified for BRAF V600 mutation using the cobas 4800 mutation test were selected who had progressed on vemurafenib (6… (full text at CIViC) PMID 25037139 · Ribas et al., 2014 · Open in CIViC | civic |
| Supports Sensitivity Response |
| 5 |
| accepted |
EID94Patients with other BRAF V600 mutations also respond well to the V600E drug dabrafenib. PMID 23463675 · Ponti et al., 2013 · Open in CIViC |
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| Vemurafenib | Melanoma | Predictive | D | Supports Sensitivity Response | 4 | accepted | EID4489In an in vitro study, the WM2664 and WM239A cell lines expressing BRAF V600D were associated with increased sensitivity to vemurafenib treatment, as compared to cell lines expressing BRAF wild-type. S… (full text at CIViC) PMID 20551065 · Yang et al., 2010 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID4488In an in vitro study, WM2664, a BRAF V600D expressing cell line, demonstrated improved sensitivity to vemurafenib treatment, compared to BRAF wild-type expressing cells. Sensitivity was determined by … (full text at CIViC) PMID 18287029 · Tsai et al., 2008 · Open in CIViC | civic |
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| 〃 | Melanoma | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID13056In this study, sustained expression of BRAF V600E in primary human melanocytes initially increased proliferation but subsequently induced stable cell-cycle arrest accompanied by senescence-associated … (full text at CIViC) PMID 16079850 · Michaloglou et al., 2005 · Open in CIViC | civic |
| 〃 | Melanoma | Oncogenic | D | Supports Oncogenicity | 2 | submitted | EID13054In this study, conditional melanocyte-specific expression of BRAF V600E in mice induced benign melanocytic hyperplasia that did not progress to melanoma during 15–20 months of follow-up. In contrast, … (full text at CIViC) PMID 19282848 · Dankort et al., 2009 · Open in CIViC | civic |
| Atezolizumab + Cobimetinib + VemurafenibCombination | Melanoma | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID13045In an exploratory biomarker analysis of the randomized, double-blind, placebo-controlled phase III IMspire150 trial (NCT02908672), 379 patients with centrally confirmed BRAF V600E-mutated, previously … (full text at CIViC) PMID 35131452 · Robert et al., 2022 · Open in CIViC | civic |
| Dabrafenib | Melanoma | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11244In an open-label, phase 3 randomized trial, 250 patients with either previously untreated, stage IV or unresectable stage III BRAF V600E mutation-positive melanoma were randomly assigned (3:1) to rece… (full text at CIViC) PMID 22735384 · Hauschild et al., 2012 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | B | Supports Sensitivity Response | — | submitted | EID2126Patients with BRAF mutations who were treated with the specific RAF inhibitor dabrafenib had an improved overall survival (P<0.003) compared to untreated patients with BRAF mutations. Patients harbori… (full text at CIViC) PMID 21343559 · Long et al., 2011 · Open in CIViC | civic |
| 〃 | Cutaneous MelanomaALIAS | Predictive | B | Supports Sensitivity Response | — | submitted | EID2146In a phase 2 clinical trial with 250 metastatic melanoma BRAF-V600E patients, treatment groups were randomly assigned to either dabrafenib, BRAF specific inhibitor, (n=187) or dacarbazine, a standard… (full text at CIViC) PMID 22735384 · Hauschild et al., 2012 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | — | submitted | EID2127Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. PMID 20818844 · Flaherty et al., 2010 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | — | submitted | EID2128An inducible BRAF-V600E mouse melanoma model shows a tight correlation between activated BRAF and disease progression. PMID 16424035 · Hoeflich et al., 2006 · Open in CIViC | civic |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | — | submitted | EID2132Proposed 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 |
| 〃 | Melanoma | Predictive | D | Supports Sensitivity Response | — | submitted | EID2133Acquired resistance to vemurafenib in BRAF-V600E positive melanomas frequently confound vemurafenib therapy. PMID 21107320 · Johannessen et al., 2010 · Open in CIViC | civic |