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Inhibiting IDO pathways to treat cancer: lessons from the ECHO-301 trial and beyond

Overview of attention for article published in Seminars in Immunopathology, September 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#34 of 333)
  • Good Attention Score compared to outputs of the same age (72nd percentile)
  • High Attention Score compared to outputs of the same age and source (83rd percentile)

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10 tweeters

Citations

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16 Dimensions

Readers on

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44 Mendeley
Title
Inhibiting IDO pathways to treat cancer: lessons from the ECHO-301 trial and beyond
Published in
Seminars in Immunopathology, September 2018
DOI 10.1007/s00281-018-0702-0
Pubmed ID
Authors

Alexander J. Muller, Mark G. Manfredi, Yousef Zakharia, George C. Prendergast

Abstract

With immunotherapy enjoying a rapid resurgence based on the achievement of durable remissions in some patients with agents that derepress immune function, commonly referred to as "checkpoint inhibitors," enormous attention developed around the IDO1 enzyme as a metabolic mediator of immune escape in cancer. In particular, outcomes of multiple phase 1/2 trials encouraged the idea that small molecule inhibitors of IDO1 may improve patient responses to anti-PD1 immune checkpoint therapy. However, recent results from ECHO-301, the first large phase 3 trial to evaluate an IDO1-selective enzyme inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in advanced melanoma, showed no indication that epacadostat provided an increased benefit. Here we discuss several caveats associated with this failed trial. First is the uncertainty as to whether the target was adequately inhibited. In particular, there remains a lack of direct evidence regarding the degree of IDO1 inhibition within the tumor, and previous trial data suggest that sufficient drug exposure may not have been achieved at the dose tested in ECHO-301. Second, while there is a mechanistic rationale for the combination tested, the preclinical data were not particularly compelling. More efficacious combinations have been demonstrated with DNA damaging modalities which may therefore be a more attractive alternative. Third, as a highly selective IDO1 inhibitor, epacadostat was advanced aggressively despite preclinical genetic evidence of tumors bypassing IDO1 blockade. Indeed, a well-grounded literature starting in 2011 points to targeting strategies that account for both IDO and tryptophan 2,3-dioxygenase as more appealing directions to pursue, including dual inhibitors and inhibitors of nodal downstream effector pathways such as aryl hydrocarbon receptor blockade. Overall, the clinical readout from a single trial with significant limitations is by no means a definitive test for the field. While biomarker information yet to be gleaned from ECHO-301 may yet reveal useful information regarding IDO1 pathway drugs, better rationalized compounds and better rationalized trial designs will be important in the future to accurately gauge medical impact.

Twitter Demographics

The data shown below were collected from the profiles of 10 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 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 44 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 32%
Unspecified 11 25%
Other 6 14%
Student > Ph. D. Student 5 11%
Student > Bachelor 2 5%
Other 6 14%
Readers by discipline Count As %
Unspecified 14 32%
Immunology and Microbiology 9 20%
Medicine and Dentistry 9 20%
Biochemistry, Genetics and Molecular Biology 3 7%
Agricultural and Biological Sciences 3 7%
Other 6 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 13 October 2018.
All research outputs
#2,236,769
of 12,793,889 outputs
Outputs from Seminars in Immunopathology
#34
of 333 outputs
Outputs of similar age
#72,696
of 267,750 outputs
Outputs of similar age from Seminars in Immunopathology
#1
of 6 outputs
Altmetric has tracked 12,793,889 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 333 research outputs from this source. They receive a mean Attention Score of 3.2. This one has done well, scoring higher than 89% 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 267,750 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them