Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2016
A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Therapeutic outcome of early-phase clinical trials in multiple myeloma: a meta-analysis.Blood cancer journal · 2021Pooled it
- Neuropeptide Precursor VGF Promotes Liver Metastatic Colonization of Gαq Mutant Uveal Melanoma by Facilitating Tumor Microenvironment via Paracrine Loops.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Combined MEK1/2 and ATR inhibition promotes myeloma cell death through a STAT3-dependent mechanism in vitro and in vivo.British journal of haematology · 2024Article
- Mucocutaneous toxicities from MEK inhibitors: a scoping review of the literature.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Multiple myeloma: signaling pathways and targeted therapy.Molecular biomedicine · 2024Review
- The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.International journal of molecular sciences · 2024Review
- Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects.Oncology research · 2024Article
- The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.Current topics in medicinal chemistry · 2024Review
- Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction.Translational oncology · 2022Article
- KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders.Cancers · 2022Review
- Review
- Review
- ActivatingProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Enhancing venetoclax activity in hematological malignancies.Expert opinion on investigational drugs · 2020Review
- ERK Regulates HIF1α-Mediated Platinum Resistance by Directly Targeting PHD2 in Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Histone deacetylase inhibition in combination with MEK or BCL-2 inhibition in multiple myeloma.Haematologica · 2019Article
- High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment.Journal of clinical medicine · 2019Review
- Future of Personalized Therapy Targeting Aberrant Signaling Pathways in Multiple Myeloma.Clinical lymphoma, myeloma & leukemia · 2019Review
- Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway.Journal of hematology & oncology · 2018Review
- The implication from RAS/RAF/ERK signaling pathway increased activation in epirubicin treated triple negative breast cancer.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma cells. This phase II study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory multiple myeloma. EXPERIMENTAL
designAZD6244 (75 mg) was administered orally, twice a day, continuously for 28-day cycles. Response was evaluated after three cycles.
resultsThirty-six patients received therapy. The median age was 65 years (range: 43-81) and the median number of prior therapies was 5 (range: 2-11). The most common grade 3 and 4 toxicities included anemia, neutropenia, thrombocytopenia, diarrhea, and fatigue. Three deaths occurred possibly related to AZD6244 (2 due to sepsis, 1 due to acute kidney injury). After AZD6244 discontinuation, three additional deaths occurred due to disease progression. The response rate (CR + PR) was 5.6% with a mean duration of response of 4.95 months and median progression-free survival time of 3.52 months. One patient had a very good partial response (VGPR), 1 patient had a partial response, 17 patients had stable disease, 13 patients had progressive disease, and 4 patients could not be assessed for response. Pharmacodynamic studies revealed variable effects on bone marrow CD138(+) cell MEK1/2 and ERK1/2 phosphorylation. The best clinical response, a prolonged VGPR, occurred in a patient with an MMSET translocation.
conclusionsSingle-agent AZD6244 was tolerable and had minimal activity in this heavily pretreated population.
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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.