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A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor

Overview of attention for article published in British Journal of Cancer, February 2017
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

blogs
1 blog
twitter
5 tweeters

Citations

dimensions_citation
26 Dimensions

Readers on

mendeley
35 Mendeley
Title
A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor
Published in
British Journal of Cancer, February 2017
DOI 10.1038/bjc.2017.10
Pubmed ID
Authors

Johanna C Bendell, Milind Javle, Tanios S Bekaii-Saab, Richard S Finn, Zev A Wainberg, Daniel A Laheru, Colin D Weekes, Benjamin R Tan, Gazala N Khan, Mark M Zalupski, Jeffrey R Infante, Suzanne Jones, Kyriakos P Papadopoulos, Anthony W Tolcher, Renae E Chavira, Janna L Christy-Bittel, Emma Barrett, Amita Patnaik

Abstract

Binimetinib (MEK162; ARRY-438162) is a potent and selective oral MEK 1/2 inhibitor. This phase 1 study determined the maximum tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and preliminary anti-tumour activity of binimetinib in patients with advanced solid tumours, with expansion cohorts of patients with biliary cancer or KRAS- or BRAF-mutant colorectal cancer. Binimetinib was administered twice daily. Expansion cohorts were enroled after MTD determination following a 3+3 dose-escalation design. Pharmacokinetic properties were determined from plasma samples. Tumour samples were assessed for mutations in RAS, RAF, and other relevant genes. Pharmacodynamic properties were evaluated in serum and skin punch biopsy samples. Ninety-three patients received binimetinib (dose-escalation phase, 19; expansion, 74). The MTD was 60 mg twice daily, with dose-limiting adverse events (AEs) of dermatitis acneiform and chorioretinopathy. The dose for expansion patients was subsequently decreased to 45 mg twice daily because of the frequency of treatment-related ocular toxicity at the MTD. Common AEs across all dose levels included rash (81%), nausea (56%), vomiting (52%), diarrhoea (51%), peripheral oedema (46%), and fatigue (43%); most were grade 1/2. Dose-proportional increases in binimetinib exposure were observed and target inhibition was demonstrated in serum and skin punch biopsy samples. Three patients with biliary cancer had objective responses (one complete and two partial). Binimetinib demonstrated a manageable safety profile, target inhibition, and dose-proportional exposure. The 45 mg twice daily dose was identified as the recommended phase 2 dose. The three objective responses in biliary cancer patients are encouraging and support further evaluation in this population.British Journal of Cancer advance online publication, 2 February 2017; doi:10.1038/bjc.2017.10 www.bjcancer.com.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 23%
Student > Ph. D. Student 5 14%
Other 5 14%
Unspecified 3 9%
Student > Master 3 9%
Other 11 31%
Readers by discipline Count As %
Medicine and Dentistry 10 29%
Pharmacology, Toxicology and Pharmaceutical Science 8 23%
Unspecified 5 14%
Biochemistry, Genetics and Molecular Biology 4 11%
Agricultural and Biological Sciences 4 11%
Other 4 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 August 2018.
All research outputs
#1,625,105
of 13,420,095 outputs
Outputs from British Journal of Cancer
#1,406
of 8,120 outputs
Outputs of similar age
#57,984
of 346,079 outputs
Outputs of similar age from British Journal of Cancer
#65
of 120 outputs
Altmetric has tracked 13,420,095 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,120 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.2. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 346,079 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 120 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.