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Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study

Overview of attention for article published in Lancet Oncology, February 2016
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257

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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Mentioned by

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32 news outlets
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1 policy source
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28 X users
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13 patents
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2 Facebook pages

Citations

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546 Dimensions

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419 Mendeley
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Title
Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study
Published in
Lancet Oncology, February 2016
DOI 10.1016/s1470-2045(15)00544-6
Pubmed ID
Authors

Scott Antonia, Sarah B Goldberg, Ani Balmanoukian, Jamie E Chaft, Rachel E Sanborn, Ashok Gupta, Rajesh Narwal, Keith Steele, Yu Gu, Joyson J Karakunnel, Naiyer A Rizvi

Abstract

PD-L1 and CTLA-4 immune checkpoints inhibit antitumour T-cell activity. Combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab might provide greater antitumour activity than either drug alone. We aimed to assess durvalumab plus tremelimumab in patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC). We did a multicentre, non-randomised, open-label, phase 1b study at five cancer centres in the USA. We enrolled immunotherapy-naive patients aged 18 years or older with confirmed locally advanced or metastatic NSCLC. We gave patients durvalumab in doses of 3 mg/kg, 10 mg/kg, 15 mg/kg, or 20 mg/kg every 4 weeks, or 10 mg/kg every 2 weeks, and tremelimumab in doses of 1 mg/kg, 3 mg/kg, or 10 mg/kg every 4 weeks for six doses then every 12 weeks for three doses. The primary endpoint of the dose-escalation phase was safety. Safety analyses were based on the as-treated population. The dose-expansion phase of the study is ongoing. This study is registered with ClinicalTrials.gov, number NCT02000947. Between Oct 28, 2013, and April 1, 2015, 102 patients were enrolled into the dose-escalation phase and received treatment. At the time of this analysis (June 1, 2015), median follow-up was 18·8 weeks (IQR 11-33). The maximum tolerated dose was exceeded in the cohort receiving durvalumab 20 mg/kg every 4 weeks plus tremelimumab 3 mg/kg, with two (30%) of six patients having a dose-limiting toxicity (one grade 3 increased aspartate aminotransferase and alanine aminotransferase and one grade 4 increased lipase). The most frequent treatment-related grade 3 and 4 adverse events were diarrhoea (11 [11%]), colitis (nine [9%]), and increased lipase (eight [8%]). Discontinuations attributable to treatment-related adverse events occurred in 29 (28%) of 102 patients. Treatment-related serious adverse events occurred in 37 (36%) of 102 patients. 22 patients died during the study, and three deaths were related to treatment. The treatment-related deaths were due to complications arising from myasthenia gravis (durvalumab 10 mg/kg every 4 weeks plus tremelimumab 1 mg/kg), pericardial effusion (durvalumab 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg), and neuromuscular disorder (durvalumab 20 mg/kg every 4 weeks plus tremelimumab 3 mg/kg). Evidence of clinical activity was noted both in patients with PD-L1-positive tumours and in those with PD-L1-negative tumours. Investigator-reported confirmed objective responses were achieved by six (23%, 95% CI 9-44) of 26 patients in the combined tremelimumab 1 mg/kg cohort, comprising two (22%, 95% CI 3-60) of nine patients with PD-L1-positive tumours and four (29%, 95% CI 8-58) of 14 patients with PD-L1-negative tumours, including those with no PD-L1 staining (four [40%, 95% CI 12-74] of ten patients). Durvalumab 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg showed a manageable tolerability profile, with antitumour activity irrespective of PD-L1 status, and was selected as the dose for phase 3 studies, which are ongoing. MedImmune.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 419 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 <1%
United States 1 <1%
France 1 <1%
Australia 1 <1%
Unknown 415 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 73 17%
Other 54 13%
Student > Ph. D. Student 40 10%
Student > Bachelor 40 10%
Student > Master 39 9%
Other 78 19%
Unknown 95 23%
Readers by discipline Count As %
Medicine and Dentistry 159 38%
Agricultural and Biological Sciences 33 8%
Biochemistry, Genetics and Molecular Biology 32 8%
Pharmacology, Toxicology and Pharmaceutical Science 23 5%
Immunology and Microbiology 18 4%
Other 49 12%
Unknown 105 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 257. 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 05 March 2024.
All research outputs
#143,599
of 25,559,053 outputs
Outputs from Lancet Oncology
#152
of 6,907 outputs
Outputs of similar age
#2,495
of 407,182 outputs
Outputs of similar age from Lancet Oncology
#2
of 136 outputs
Altmetric has tracked 25,559,053 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 6,907 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 35.2. This one has done particularly well, scoring higher than 97% 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 407,182 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 136 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.