Trial reportThe New England journal of medicine2012
Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations.
Trial report in The New England journal of medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1,332 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the BRAF Inhibitor GSK2118436 in Combination With the MEK Inhibitor GSK1120212 in Subjects With BRAF Mutant Metastatic Melanoma
Neoadjuvant Use of Talimogene Laherparepvec and BRAF/MEK Inhibitor for Advanced Nodal BRAF Mutant Melanoma: A Pilot Study
Who cites it
1,332 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- BRAF-targeted therapy in non-melanomatous BRAF-mutant tumours: a systematic review of broad but histology-modulated efficacy.International journal of clinical oncology · 2026Pooled it
- BRAF/MEK inhibitors for redifferentiation in patients with radioiodine refractory thyroid cancer: A systematic review and Meta-Analysis.Endocrine · 2026Pooled it
- ESMO-ESTRO consensus statements on the safety of combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors.ESMO open · 2026Pooled it
- Defining the Prognostic Significance of BRAF V600E in Early-Stage Colon Cancer: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2025Pooled it
- Safety and Efficacy Analysis of Targeted and Immune Combination Therapy in Advanced Melanoma-A Systematic Review and Network Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).ESMO open · 2025Trial
- Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development.Molecular cancer · 2024Trial
- Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial.Nature communications · 2024Trial
- BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.The New England journal of medicine · 2023Trial
- Review
- Special Issue 'Molecular Mechanisms and New Markers of Cancer'-From Static Biomarkers to Context-Aware Precision Oncology.International journal of molecular sciences · 2026Article
- PredictedInternational journal of molecular sciences · 2026Article
- Cardiac Monitoring for Patients Undergoing Treatment With MEK Inhibitor Monotherapy.Current oncology reports · 2026Review
- Precision Medicine in Dermatology: MEK Inhibition and MAPK Pathway Modulation for Congenital Melanocytic Nevi.Biomedicines · 2026Review
- Article
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- Recent Developments and Structure-Activity Relationships of BRAF Inhibitors for Cancer Drug Discovery.Archiv der Pharmazie · 2026Review
- New Treatment Strategy and Future Research Direction for BRAF-Mutated Cancer.Cancer science · 2026Review
- Real-World Treatment Patterns in Advanced Cutaneous Melanoma in the USA.Targeted oncology · 2026Observational
- Cutaneous Adverse Drug Reactions Associated With BRAF and MEK Inhibitors: A Real-World Analysis of WHO Pharmacovigilance Data.Clinical pharmacology and therapeutics · 2026Article
1,272 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors.
Funding
Abstract
backgroundResistance to therapy with BRAF kinase inhibitors is associated with reactivation of the mitogen-activated protein kinase (MAPK) pathway. To address this problem, we conducted a phase 1 and 2 trial of combined treatment with dabrafenib, a selective BRAF inhibitor, and trametinib, a selective MAPK kinase (MEK) inhibitor.
methodsIn this open-label study involving 247 patients with metastatic melanoma and BRAF V600 mutations, we evaluated the pharmacokinetic activity and safety of oral dabrafenib (75 or 150 mg twice daily) and trametinib (1, 1.5, or 2 mg daily) in 85 patients and then randomly assigned 162 patients to receive combination therapy with dabrafenib (150 mg) plus trametinib (1 or 2 mg) or dabrafenib monotherapy. The primary end points were the incidence of cutaneous squamous-cell carcinoma, survival free of melanoma progression, and response. Secondary end points were overall survival and pharmacokinetic activity.
resultsDose-limiting toxic effects were infrequently observed in patients receiving combination therapy with 150 mg of dabrafenib and 2 mg of trametinib (combination 150/2). Cutaneous squamous-cell carcinoma was seen in 7% of patients receiving combination 150/2 and in 19% receiving monotherapy (P=0.09), whereas pyrexia was more common in the combination 150/2 group than in the monotherapy group (71% vs. 26%). Median progression-free survival in the combination 150/2 group was 9.4 months, as compared with 5.8 months in the monotherapy group (hazard ratio for progression or death, 0.39; 95% confidence interval, 0.25 to 0.62; P<0.001). The rate of complete or partial response with combination 150/2 therapy was 76%, as compared with 54% with monotherapy (P=0.03).
conclusionsDabrafenib and trametinib were safely combined at full monotherapy doses. The rate of pyrexia was increased with combination therapy, whereas the rate of proliferative skin lesions was nonsignificantly reduced. Progression-free survival was significantly improved. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01072175.).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.