Loading cancer entity…
Loading cancer entity…
Variants & evidence
20 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 |
|---|---|---|---|---|---|---|---|---|
| ARAF Mutation1 | ||||||||
| Cobimetinib | Langerhans Cell Histiocytosis | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11297In an open-label, phase II trial, 18 patients with histiocytosis, including two patients with Langerhans cell histiocytosis, of any mutational status were enrolled. Patients received cobimetinib at a … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | civic |
| ARAF Mutation + ARAF P216A + ARAF S225V1 | ||||||||
| Cobimetinib | Erdheim-Chester Disease | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11296In an open-label, phase II trial, 18 patients with histiocytosis, including 12 patients with Erdheim-Chester disease, one patient with ARAF S225V, and one patient with ARAF P216A, of any mutational st… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | civic |
| BRAF N486_P4901 | ||||||||
| Trametinib | Langerhans Cell Histiocytosis | Predictive | C | Supports Sensitivity Response | 4 | submitted | EID11300In this case series, 3 patients with Langerhans cell histiocytosis (LCH) were studied. Patient #1 was a 15-year-old male who has experienced five reactivations of LCH. He presented with left mastoid L… (full text at CIViC) PMID 32991018 · Messinger et al., 2020 · Open in CIViC | civic |
| BRAF Non-V6002 | ||||||||
| Cobimetinib | Erdheim-Chester Disease | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11298In an open-label, phase II trial, 18 patients with histiocytosis, including 12 patients with Erdheim-Chester disease with one patient having a non-V600 BRAF mutation, of any mutational status were enr… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | civic |
| 〃 | Langerhans Cell Histiocytosis | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11299In an open-label, phase II trial, 18 patients with histiocytosis, including two patients with Langerhans cell histiocytosis, with one patient having a non-V600 BRAF mutation, of any mutational status … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | civic |
| BRAF V6004 | ||||||||
| Dabrafenib/Trametinib Regimen | Histiocytic Sarcoma | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID12769An 8-year-old girl presented with secondary BRAF V600-mutant histiocytic sarcoma following T-cell acute lymphoblastic leukemia. After the poor response to initial salvage chemotherapy, the patient res… (full text at CIViC) PMID 40057687 · Tan et al., 2025 · Open in CIViC | civic |
| Vemurafenib | Erdheim-Chester Disease | Predictive | A | Supports Sensitivity Response | 5 | submitted | EID11237In this histology-independent, phase 2, open-label study, 26 patients (22 with Erdheim-Chester disease (ECD) and 4 Langerhans cell histiocytosis (LCH)) were administered 960 mg, twice daily doses of v… (full text at CIViC) PMID 29188284 · Diamond et al., 2018 · Open in CIViC | civic |
| 〃 | Langerhans Cell Histiocytosis | Predictive | B | Supports Sensitivity Response | ||||
| BRAF V600E2 | ||||||||
| Dabrafenib | Langerhans Cell Histiocytosis | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11303In this case series, 11 patients with ECD or ECD/LCH (Seven had ECD and four had overlapped ECD/LCH) were treated with single-agent dabrafenib as initial histiocytosis therapy, following the failure o… (full text at CIViC) PMID 29472347 · Bhatia et al., 2018 · Open in CIViC | civic |
| Vemurafenib | Langerhans Cell Sarcoma | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7583Off-label use of vemurafenib to treat BRAF V600E mutation-positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated. Fifty-four patients from 12 countries were treated with vem… (full text at CIViC) PMID 31513482 · Donadieu et al., 2019 · Open in CIViC | civic |
| BRAF V600K1 | ||||||||
| Dabrafenib/Trametinib Regimen | Histiocytic Sarcoma | Predictive | C | Supports Sensitivity Response | 2 | rejected | EID12770An 8-year-old girl presented with secondary BRAF V600-mutant histiocytic sarcoma following T-cell acute lymphoblastic leukemia. After the poor response to initial salvage chemotherapy, the patient res… (full text at CIViC) PMID 40057687 · Tan et al., 2025 · Open in CIViC | civic |
| BRAF V600R1 | ||||||||
| Dabrafenib/Trametinib Regimen | Histiocytic Sarcoma | Predictive | C | Supports Sensitivity Response | 2 | rejected | EID12771An 8-year-old girl presented with secondary BRAF V600-mutant histiocytic sarcoma following T-cell acute lymphoblastic leukemia. After the poor response to initial salvage chemotherapy, the patient res… (full text at CIViC) PMID 40057687 · Tan et al., 2025 · Open in CIViC | civic |
| MAP2K1 56_61QKQKVG>R1 | ||||||||
| Trametinib | Langerhans Cell Histiocytosis | Predictive | D | Supports Resistance | 3 | submitted | EID6384The C121S/G128D and 56_61QKQKVG>R variants were resistant to the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib in vitro. All three variant proteins constitutively phosphorylated E… (full text at CIViC) PMID 25899310 · Nelson et al., 2015 · Open in CIViC | civic |
| MAP2K1 C121S + MAP2K1 G128D1 | ||||||||
| Trametinib | Langerhans Cell Histiocytosis | Predictive | D | Supports Resistance | 3 | submitted | EID6385The C121S/G128D and 56_61QKQKVG>R variants were resistant to the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib in vitro. All three variant proteins constitutively phosphorylated E… (full text at CIViC) PMID 25899310 · Nelson et al., 2015 · Open in CIViC | civic |
| MAP2K1 E102_I103delEI1 | ||||||||
| Trametinib | Langerhans Cell Histiocytosis | Predictive | C | Supports Sensitivity Response | 5 | submitted | EID6447Brown wt al. described ex vivo efficacy of MEK inhibition in tissue obtained from a LCH patient harboring this somatic MAP2K1 mutation. We have treated a single patient with a systemic LCH showing th… (full text at CIViC) PMID 24982505 · Brown et al., 2014 · Open in CIViC | civic |
| MAP2K1 K57_G61del1 | ||||||||
| Trametinib | Langerhans Cell Histiocytosis | Predictive | C | Supports Sensitivity Response | 4 | submitted | EID11301In this case series, 3 patients with Langerhans cell histiocytosis (LCH) were studied. Patient #1 was a 15-year-old male who has experienced five reactivations of LCH. He presented with left mastoid L… (full text at CIViC) PMID 32991018 · Messinger et al., 2020 · Open in CIViC | civic |
| BRAF Fusion1 | ||||||||
| BRAF Inhibitor + TunlametinibSubstitutes | Langerhans Cell Histiocytosis | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8030Novel BRAF gene fusion in Langerhans Cell Histiocytosis lesions results in constitutive ERK activation that is responsive to second-generation BRAF and MEK inhibitors, but not to a BRAF-V600E inhibito… (full text at CIViC) PMID 27729324 · Chakraborty et al., 2016 · Open in CIViC | civic |
| KRAS Mutation + MAP2K1 Mutation + MAP2K2 Mutation + NRAS Mutation + RAF1 MutationRAF1MAP2K1MAP2K2KRASNRAS2 | ||||||||
| Cobimetinib | Erdheim-Chester Disease | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11328In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. The overall response rate was 89% (90% CI: 73 - 100). Responses were durable, with no acquired … (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | civic |
| 〃 | Langerhans Cell Histiocytosis | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11329In an open-label, phase II trial, 18 patients with histiocytosis of any mutational status were enrolled. Patients received cobimetinib at a starting dose of 60 mg daily for 21 days of each 28-day cycl… (full text at CIViC) PMID 30867592 · Diamond et al., 2019 · Open in CIViC | |
Data updated 2 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.
| 4 |
| submitted |
EID11302In this open-label, non-randomized trial, 26 patients with BRAF V600–mutant Erdheim-Chester Disease or Langerhans Cell Histiocytosis (22 with Erdheim-Chester Disease, 4 with Langerhans Cell Histiocyto… (full text at CIViC) PMID 29188284 · Diamond et al., 2018 · Open in CIViC |
| civic |
| 〃 | Langerhans Cell Histiocytosis | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1575Patients with BRAF-V600 mutated cancers were identified (n=122) and clinical response to vemurafenib was evaluated. Of the 14 patients with Langerhans’-cell histiocytosis, 43% of patients had a respo… (full text at CIViC) PMID 26287849 · Hyman et al., 2015 · Open in CIViC | civic |
| civic |