Trial reportNature communications2021
Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial.
Trial report in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02583516 (A Randomized Phase II Study of Vemurafenib Plus Cobimetinib Continuous Versus Intermittent, in Previously Untreated BRAFV600- Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma), which is not on this map. Cited by 34 papers.
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.
A Randomized Phase II Study of Vemurafenib Plus Cobimetinib Continuous Versus Intermittent, in Previously Untreated BRAFV600- Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Practical management of BRAF inhibitors in glioma: toxicity and resistance.CNS oncology · 2026Review
- Tempered optimism: Advances in the precision medicine era for pediatric low-grade glioma.Neuro-oncology · 2026Review
- Cardiac Monitoring for Patients Undergoing Treatment With MEK Inhibitor Monotherapy.Current oncology reports · 2026Review
- TFAP2A links drug resistance to antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Plasticity, signaling, and metabolic rewiring in melanoma persister cells.Communications biology · 2026Review
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Multidimensional tumor heterogeneity and its role in therapeutic resistance.Frontiers in immunology · 2026Review
- ATAD2 drives melanoma growth and progression and inhibits ferroptosis.EMBO reports · 2026Article
- Retreatment and rechallenge with BRAF/MEK inhibitors in patients with metastatic melanoma: results from the real-world Spanish Melanoma Registry (GEM-1801).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Observational
- Review
- Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- RAF inhibitor re-challenge therapy in BRAF-aberrant pan-cancers: the RE-RAFFLE study.Molecular cancer · 2024Observational
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Pediatric low-grade glioma: State-of-the-art and ongoing challenges.Neuro-oncology · 2024Review
- The role of MEK inhibition in pediatric low-grade gliomas.Frontiers in oncology · 2024Review
- Drug-tolerant persister cells in cancer: the cutting edges and future directions.Nature reviews. Clinical oncology · 2023Review
- Evolutionary Dynamics and Intermittent Therapy for Metastatic Cancers.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 17 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases.
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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.