Trial reportCancer2016
Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib in RAS-mutant relapsed or refractory myeloid malignancies.
Trial report in Cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 89 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches.Frontiers in oncology · 2021Pooled it
- Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.Breast cancer research and treatment · 2025Trial
- Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium.Cancer discovery · 2021Trial
- Oral MEK 1/2 Inhibitor Trametinib in Combination With AKT Inhibitor GSK2141795 in Patients With Acute Myeloid Leukemia With RAS Mutations: A Phase II Study.Clinical lymphoma, myeloma & leukemia · 2019Trial
- Phase II Trial of MEK Inhibitor Binimetinib (MEK162) in RAS-mutant Acute Myeloid Leukemia.Clinical lymphoma, myeloma & leukemia · 2019Trial
- Validation of the 2017 revision of the WHO chronic myelomonocytic leukemia categories.Blood advances · 2018Trial
- Long-term outcomes inHaematologica · 2026Article
- Clinico-genomic characterization of RAS-mutant acute myeloid leukemia.Annals of hematology · 2026Article
- Article
- Targeting MET and KRAS G12C co-occurring mutation in metastatic adenoid cystic carcinoma of the trachea: a case report.Journal of medical case reports · 2025Article
- Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia.bioRxiv : the preprint server for biology · 2025Article
- Integrating multi-omics methods for personalized treatment of refractory chronic myelomonocytic leukemia withCancer pathogenesis and therapy · 2025Article
- Article
- Activity of trametinib as maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory RAS pathway-mutated hematologic malignancies.Annals of hematology · 2025Article
- Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.Biomedicines · 2025Review
- Chronic Neutrophilic Leukemia: Advances in Diagnosis, Genetic Insights, and Management Strategies.Cancers · 2025Review
- Chronic myelomonocytic leukemia: molecular pathogenesis and therapeutic innovations.Haematologica · 2025Review
- Genomic Landscape of Myelodysplastic/Myeloproliferative Neoplasms: A Multi-Central Study.International journal of molecular sciences · 2024Article
- Trametinib Sensitivity is Defined by a Myeloid Differentiation Profile in Acute Myeloid Leukemia.Drugs in R&D · 2024Article
- Molecular Features and Treatment Paradigms of Acute Myeloid Leukemia.Biomedicines · 2024Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedErratum.2016
Authors and funding
21 authors at 16 institutions in 3 countries.
Funding
Abstract
backgroundRAS/RAF/mitogen-activated protein kinase activation is common in myeloid malignancies. Trametinib, a mitogen-activated protein kinase kinase 1 (MEK1)/MEK2 inhibitor with activity against multiple myeloid cell lines at low nanomolar concentrations, was evaluated for safety and clinical activity in patients with relapsed/refractory leukemias.
methodsThis phase 1/2 study accrued patients with any relapsed/refractory leukemia in phase 1. In phase 2, this study accrued patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) with NRAS or KRAS mutations (cohort 1); patients with AML, MDS, or chronic myelomonocytic leukemia (CMML) with a RAS wild-type mutation or an unknown mutation status (cohort 2); and patients with CMML with an NRAS or KRAS mutation (cohorts 3).
resultsThe most commonly reported treatment-related adverse events were diarrhea, rash, nausea, and increased alanine aminotransferase levels. The phase 2 recommended dose for Trametinib was 2 mg orally daily. The overall response rates were 20%, 3%, and 27% for cohorts 1, 2, and 3, respectively, and this indicated preferential activity among RAS-mutated myeloid malignancies. Repeated cycles of trametinib were well tolerated with manageable or reversible toxicities; these results were similar to those of other trametinib studies.
conclusionsThe selective, single-agent activity of trametinib against RAS-mutated myeloid malignancies validates its therapeutic potential. Combination strategies based on a better understanding of the hierarchical role of mutations and signaling in myeloid malignancies are likely to improve the response rate and duration. Cancer 2016;122:1871-9. © 2016 American Cancer Society.
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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.