Evidence map›Paper›PMID 35677320›Full record

ArticleTherapeutic advances in medical oncology2022

Improving the tolerability of osimertinib by identifying its toxic limit.

Bram C Agema, G D Marijn Veerman, Christi M J Steendam, Daan A C Lanser, Tim Preijers, Cor van der Leest, Birgit C P Koch, Anne-Marie C Dingemans, Ron H J Mathijssen, Stijn L W Koolen

Open access · goldAbstract read
In one paragraph

Article in Therapeutic advances in medical oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% of its field
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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Bram C AgemaDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, Rotterdam 3015 GD, The Netherlands Department of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
G D Marijn VeermanDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
Christi M J SteendamDepartment of Pulmonology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0002-8487-9344
Daan A C LanserDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
Tim PreijersDepartment of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
Cor van der LeestDepartment of Pulmonology, Amphia Hospital, Breda, The Netherlands.
Birgit C P KochDepartment of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
Anne-Marie C DingemansDepartment of Pulmonology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
Ron H J MathijssenDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
Stijn L W KoolenDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Clinical Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
Erasmus MC · NLAmphia Ziekenhuis · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand. Therefore, we aimed to study the relationship between osimertinib exposure and severe toxicity and to identify a safe toxic limit for a preventive dose reduction. Methods: In this real-life prospective cohort study, patients with NSCLC treated with osimertinib were followed for severe toxicity (grade ⩾3 toxicity, dose reduction or discontinuation, hospital admission, or treatment termination). Blood for pharmacokinetic analyses was withdrawn during every out-patient visit. Primary endpoint was the correlation between osimertinib clearance (exposure) and severe toxicity. Secondary endpoint was the exposure-efficacy relationship, defined as progression-free survival (PFS) and overall survival (OS). Results: In total, 819 samples from 159 patients were included in the analysis. Multivariate competing risk analysis showed osimertinib clearance ( Conclusion: Osimertinib exposure is highly correlated with the occurrence of severe toxicity. To optimize tolerability, patients above the toxic limit concentration of 259 ng/mL could benefit from a preventive dose reduction, without fear for diminished effectiveness.

Indexed as

exposure–efficacy relationshipexposure–toxicity relationshipNSCLCosimertinibpreventive dose reduction

Identifiers

PMID35677320
PMCPMC9168866
OpenAlexW4285292056

What OpenQuestion holds

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LicenceCC BY
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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.