Evidence map›Paper›PMID 38665845›Full record

ArticleTherapeutic advances in medical oncology2024

Improving olaparib exposure to optimize adverse effects management.

Marylise Sterlé, Alicja Puszkiel, Chloé Burlot, Eva Pereira, Audrey Bellesoeur, Sixtine De Percin, Guillaume Beinse, Jean-David Fumet, Laure Favier, Julie Niogret and 4 more

Open access · goldAbstract read
In one paragraph

Article in Therapeutic advances in medical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 40% 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

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Review
  2. Article
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

14 authors at 5 institutions in 1 country.

Marylise SterléPharmacy Department, Centre Georges-François Leclerc, Dijon, France.ORCID https://orcid.org/0009-0000-0645-8934
Alicja PuszkielBiologie du Médicament - Toxicologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Chloé BurlotPharmacy Department, Centre Georges-François Leclerc, Dijon, France.ORCID https://orcid.org/0000-0001-9779-6591
Eva PereiraBiologie du Médicament - Toxicologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Audrey BellesoeurInstitut Curie, Département d'Oncologie Médicale, Paris, France.
Sixtine De PercinOncology Department, Cochin Hospital (AP-HP), CARPEM, Paris, France.
Guillaume BeinseOncology Department, Cochin Hospital (AP-HP), CARPEM, Paris, France.
Jean-David FumetOncology Department, Centre Georges-François Leclerc, INSERM U1231, UFR des Sciences de Santé, Dijon, France.
Laure FavierOncology Department, Centre Georges-François Leclerc, INSERM U1231, UFR des Sciences de Santé, Dijon, France.
Julie NiogretOncology Department, Centre Georges-François Leclerc, INSERM U1231, UFR des Sciences de Santé, Dijon, France.
Benoit BlanchetBiologie du Médicament - Toxicologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Bernard RoyerPharmacology and Toxicology Laboratory, CHRU Besançon, Besançon, France.
Leïla Bengrine-LefevreOncology Department, Centre Georges-François Leclerc, INSERM U1231, UFR des Sciences de Santé, Dijon, France.
Antonin SchmittPharmacy Department, Centre Georges-François Leclerc, 1 rue Pr Marion, Dijon 21079, France.ORCID https://orcid.org/0000-0002-3132-7730
Inserm · FRHôpital Cochin · FRCentre Hospitalier Universitaire de Besançon · FRInstitut Curie · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Olaparib is an inhibitor of the human poly-(ADP-ribose)-polymerase enzymes (PARP1/2) needed to repair single-strand DNA breaks. It is used in breast, ovarian, prostate and pancreatic cancer. Objectives: This work aimed to describe the pharmacokinetics/pharmacodynamics (PK/PD) relationship between olaparib plasma concentrations and common adverse effects (i.e. anaemia and hypercreatininaemia), in a real-life setting, to propose a target concentration for therapeutic drug monitoring. Methods: Two PK/PD models describing the evolution of haemoglobinaemia and creatininaemia as a function of time were developed, based on data from, respectively, 38 and 37 patients receiving olaparib. The final model estimates were used to calculate the incidence of anaemia and creatinine increase according to plasma trough concentrations for 1000 virtual subjects to define target exposure. Results: The final models correctly described the temporal evolution of haemoglobinaemia and creatininaemia for all patients. The haemoglobinaemia PK/PD model is inspired by Friberg's model, and the creatininaemia PK/PD model is an indirect response model. Model parameters were in agreement with physiological values and close to literature values for similar models. The mean (population) plasma haemoglobin concentration at treatment initiation, as estimated by the model, was 11.62 g/dL, while creatinine concentration was 71.91 µmol/L. Using simulations, we have identified a target trough concentration of 3500-4000 ng/mL, above which more than 20% of patients would report grade ≥3 anaemia. Conclusion: Based on real-world data, we were able to properly describe the time course of haemoglobinaemia and plasma creatininaemia during olaparib treatment.

Indexed as

anaemiacreatinine increasemodellingolaparibovarian cancerPK/PD

Identifiers

PMID38665845
PMCPMC11044803
OpenAlexW4395479243

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.