Evidence map›Paper›PMID 34545619›Full record

ArticleBritish journal of clinical pharmacology2022

Pharmacokinetically-guided dosing to improve the efficacy of brigatinib in non-small cell lung cancer patients.

Simon E Koele, Stijn W van Beek, Anthonie J van der Wekken, Berber Piet, Michel M van den Heuvel, Rob Ter Heine

Abstract read
In one paragraph

Article in British journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Simon E KoeleDepartment of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0002-7011-667X
Stijn W van BeekDepartment of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Anthonie J van der WekkenDepartment of Pulmonary Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Berber PietDepartment of Pulmonology, Radboud University Medical Center, Nijmegen, the Netherlands.
Michel M van den HeuvelDepartment of Pulmonology, Radboud University Medical Center, Nijmegen, the Netherlands.
Rob Ter HeineDepartment of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0003-2185-8201

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Brigatinib was recently approved for the treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer and is dosed according to a one-dose-fits-all paradigm. We aimed to identify a pharmacokinetically-guided precision dosing strategy to improve treatment response with brigatinib through simulations using a previously published pharmacokinetic-pharmacodynamic model. Dosing strategies explored were the approved 180 mg QD; the highest tolerable dose tested in clinical trials: 240 mg QD; and two precision dosing strategies targeting the median trough concentrations following 180 mg QD, and 240 mg QD. We investigated the impact of alternative dosing regimens on progression-free survival (PFS), overall survival (OS) and the probability of developing a grade ≥2 rash or grade ≥2 amylase increase. Median PFS and OS increased by 1.6 and 7.8 months, respectively between the currently approved dosing strategy and precision dosing to the median trough concentration of the 240 mg dosing strategy, with only a minor increase in the probability of developing toxicity.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAnaplastic Lymphoma KinaseHumansOrganophosphorus CompoundsProtein Kinase InhibitorsPyrimidinesAnaplastic Lymphoma KinasebrigatinibOrganophosphorus CompoundsProtein Kinase InhibitorsPyrimidinesbrigatinibnon-small cell lung cancerpharmacokinetic-pharmacodynamicpharmacometricsprecision dosingsimulationtherapeutic drug monitoring

Identifiers

PMID34545619
PMCPMC9292371

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Registered trials

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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.