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Association details:
| Biomarker: | BRAF V600E |
|---|---|
| Cancer: | Melanoma |
| Drug: | Zelboraf (vemurafenib) (BRAF inhibitor, BRAF V600E inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Excerpt:
ZELBORAF is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.
Source:
Title:
Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation
Excerpt:
A phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation....At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group....Response rates were 48% for vemurafenib and 5% for dacarbazine….Vemurafenib produced improved rates of overall and progression free survival in patients with previously untreated melanoma with the BRAF V600E mutation.
Secondary therapy:
dacarbazine
DOI:
10.1056/NEJMoa1103782
Trial ID:
Source:
Title:
A Study of RO5185426 in Patients With Metastatic Melanoma
Excerpt:
...- Histologically confirmed metastatic melanoma with documented BRAF V600E mutation, determined by the cobas BRAF V600 mutation test...
Trial ID:
Source:
Title:
Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E
Excerpt:
...- Histologically-confirmed metastatic melanoma (unresectable Stage IIIc or IV) with an activating BRAF mutation other than V600E, as detected by DNA sequencing of exon 15 performed at a centralized laboratory...
Trial ID:
More C2 evidence
Source:
Title:
A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients
Excerpt:
...Patients with histological confirmed BRAFV600E melanoma (Stage IIIC or Stage IV, American Joint Commission on Cancer); 3....
Trial ID:
Source:
Title:
A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)
Excerpt:
...- positive for BRAF V600E mutation...
Trial ID:
Source:
Title:
A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma
Excerpt:
...- Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test...
Trial ID:
Source:
Title:
Phase 2 Study of Neoadjuvant Vemurafenib in Melanoma Patients With Untreated Brain Metastases
Excerpt:
...- Biopsy proven metastatic melanoma with the B-raf V600E or V600K mutations....
Trial ID:
Source:
Title:
A Study of Vemurafenib in Previously Treated Patients With Metastatic Melanoma
Excerpt:
...- BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)...
Trial ID:
Source:
Title:
Safety Study of PLX4032 in Patients With Solid Tumors
Excerpt:
...- Patients from whom paired melanoma biopsies are planned must have a V600E+ BRAF mutation confirmed prior to the administration of PLX4032...
Trial ID:
Source:
Title:
The Safety and Efficacy Study of Vemurafenib (CT) Compared With Vemurafenib (Zelbolaf®) in Advanced Patients Harboring the V600 BRAF Mutation
Excerpt:
...- Signed written informed consent - Recheck the results of histological studies and paraffin blocks - Histologically confirmed cancer that is either Stage IIIc (unresectable) or ---Stage IV (metastatic), and determined to be BRAF V600E or V600K mutation-positive by the local laboratory. ...
Source:
Title:
A Phase I Trial of Vemurafenib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma
Excerpt:
...- Patients must have histologically confirmed diagnosis of Stege IV metastic melanoma positive for BRAF V600E mutation by either the COBAS test or other CLIA approved assay....
Trial ID:
Source:
Title:
A Pharmacokinetic and Metabolism Study of 14C-labeled RO5185426 on Patients With Metastatic Melanoma
Excerpt:
...- Positive BRAF V600E mutation result (by Roche CoDx test)...
Trial ID:
Source:
Title:
A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma
Excerpt:
...- positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)...
Trial ID:
Source:
Title:
Vemurafenib (R05185426) in Poor Performance Status Patients With Unresectable Locally Advanced or Metastatic Melanoma Harboring a V600E/K Mutation
Excerpt:
...- A confirmed EBRAFV600E or KBRAFV600K mutation....
Trial ID:
Less C2 evidence
Source:
Title:
P-126 Efficacy of neoadjuvant targeted therapy for resectable stage IIIB-D or IV BRAF V600 mutation-positive melanoma – real world evidence
Published date:
04/15/2021
Excerpt:
Patients (pts) with marginally resectable bulky stage III or resectable stage IV histologically confirmed melanoma were enrolled. BRAF V600 mutation status and pathology were confirmed...23 pts were treated with dabrafenib and trametinib, 3 pts were treated with vemurafenib and cobimetinib, and 3 with vemurafenib monotherapy.... BRAFi/MEKi combination is an effective and safe regimen in the perioperative treatment of melanoma.
Source:
Title:
Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib?±?cobimetinib: a pooled analysis of four clinical trials
Published date:
08/03/2020
Excerpt:
Recursive partitioning analysis (RPA) was performed to model relationships between prespecified covariates and ppOS in patients with BRAFV600-mutated metastatic melanoma who had experienced progressive disease (PD) following treatment with cobimetinib plus vemurafenib, vemurafenib monotherapy, or dacarbazine in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies....Across treatment cohorts, patients treated with immunotherapy or targeted therapy after PD had better ppOS than those given other treatments....
Secondary therapy:
dacarbazine
DOI:
https://doi.org/10.1186/s12967-020-02458-x
Source:
Title:
Inhibition of mutated, activated BRAF in metastatic melanoma
Excerpt:
Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients.
DOI:
10.1056/NEJMoa1002011
Source:
Title:
BRAF Inhibitor Resistance Mechanisms in Metastatic Melanoma: Spectrum and Clinical Impact
Excerpt:
Twenty patients had BRAFV600E (67%), 9 had BRAFV600K (30%), and 1 had BRAFV600R melanoma (3%). Nearly all (28 of 30; 93%) patients experienced tumor regression with treatment. The median PFS was 22.0 weeks [95% confidence interval (CI), 13.0–31.0) and the median OS was 80.7 weeks (95% CI, 46.0–115.4; Table 1).
DOI:
10.1158/1078-0432.CCR-13-3122
Trial ID:
Source:
Title:
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Excerpt:
Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation.
Secondary therapy:
dacarbazine
DOI:
10.1056/NEJMoa1103782
Trial ID:
Source:
Title:
USP18 enhances the resistance of BRAF-mutated melanoma cells to vemurafenib by stabilizing cGAS expression to induce cell autophagy
Excerpt:
CONTRADICTING EVIDENCE: The cancer tissues of BRAF V600E mutant melanoma patients before and after vemurafenib treatment were collected...In vivo experimentations confirmed that USP18 promoted vemurafenib-induced protective autophagy...which promoted resistance to vemurafenib in BRAF V600E mutant melanoma cells.
DOI:
https://doi.org/10.1016/j.intimp.2023.110617
Source:
Title:
An integrated model of RAF inhibitor action predicts inhibitor activity against oncogenic BRAF signaling
Excerpt:
Furthermore, VEM suppressed cell growth selectively in BRAFV600E melanoma cells, whereas TAK showed effectiveness in both melanomas and colorectal cells. We first treated two BRAFV600E melanoma cell lines with VEM and resistant clones started developing after about 4 weeks. In contrast, no resistant colonies developed in treatments including TAK,
DOI:
10.1016/j.ccell.2016.06.024
Source:
Title:
RG7204 (PLX4032), a Selective BRAFV600E Inhibitor, Displays Potent Antitumor Activity in Preclinical Melanoma Models
Excerpt:
In conclusion, RG7204 has shown potent antitumor activity in preclinical melanoma models in which mutant BRAFV600E is expressed.
DOI:
10.1158/0008-5472.CAN-10-0646
Source:
Title:
Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors
Excerpt:
To test whether ERK blockade was efficacious in the context of these clinically observed resistance mechanisms, stable cell lines expressing each of these variants were engineered in a BRAFV600E A375 background. As shown in Fig. 3D, overexpression of KRASG13D (positive control), BRAFV600E (to simulate amplification), or BRAFV600EΔ2-8 all conferred resistance to PLX4032...
DOI:
10.1158/2159-8290.CD-13-0070
