Evidence map›Paper›PMID 35890213›Full record

ArticlePharmaceutics2022

Population Pharmacokinetics of Palbociclib and Its Correlation with Clinical Efficacy and Safety in Patients with Advanced Breast Cancer.

Perrine Courlet, Evelina Cardoso, Carole Bandiera, Athina Stravodimou, Jean-Philippe Zurcher, Haithem Chtioui, Isabella Locatelli, Laurent Arthur Decosterd, Léa Darnaud, Benoit Blanchet and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. 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

16 authors at 7 institutions in 2 countries.

Perrine CourletCentre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.ORCID 0000-0001-9114-7793
Evelina CardosoSchool of Pharmaceutical Sciences, University of Geneva, 1206 Geneva, Switzerland.
Carole BandieraSchool of Pharmaceutical Sciences, University of Geneva, 1206 Geneva, Switzerland.ORCID 0000-0002-9996-3100
Athina StravodimouBreast Center, Department of Oncology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
Jean-Philippe ZurcherBreast Center, Department of Oncology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
Haithem ChtiouiService of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
Isabella LocatelliCenter for Primary Care and Public Health (Unisanté), University of Lausanne, 1011 Lausanne, Switzerland.ORCID 0000-0003-0870-1461
Laurent Arthur DecosterdService of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
Léa DarnaudDepartment of Pharmacokinetics and Pharmacochemistry, Cochin Hospital, AP-HP, CARPEM, AP-HP, CARPEM, 75014 Paris, France.
Benoit BlanchetDepartment of Pharmacokinetics and Pharmacochemistry, Cochin Hospital, AP-HP, CARPEM, AP-HP, CARPEM, 75014 Paris, France.
Jérôme AlexandreDepartment of Medical Oncology, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.
Anna Dorothea WagnerBreast Center, Department of Oncology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
Khalil ZamanBreast Center, Department of Oncology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.ORCID 0000-0002-2997-527X
Marie Paule SchneiderSchool of Pharmaceutical Sciences, University of Geneva, 1206 Geneva, Switzerland.
Monia GuidiCentre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.ORCID 0000-0002-6419-9317
Chantal CsajkaCentre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.ORCID 0000-0002-0660-082X
Breast Center · CHUniversity of Geneva · CHUniversity of Lausanne · CHAssistance Publique – Hôpitaux de Paris · FRCentre National de la Recherche Scientifique · FRCentre universitaire de médecine générale et santé publique, Lausanne · CHHôpital Cochin · FR

Funding

Swiss Cancer Research Foundation grant HSR-4077-11-2016
6 · The paper itself

Abstract

Neutropenia is the most frequent dose-limiting toxicity reported in patients with metastatic breast cancer receiving palbociclib. The objective of this study was to investigate the pharmacokinetic-pharmacodynamic (PK/PD) relationships for toxicity (i.e., absolute neutrophil count, ANC) and efficacy (i.e., progression-free survival, PFS). A semi-mechanistic PK/PD model was used to predict neutrophils' time course using a population approach (NONMEM). Influence of demographic and clinical characteristics was evaluated. Cox proportional hazards models were developed to evaluate the influence of palbociclib PK on PFS. A two-compartment model with first-order absorption and a lag time adequately described the 255 palbociclib concentrations provided by 44 patients. The effect of the co-administration of proton-pump inhibitors in fasting conditions increased palbociclib clearance by 56%. None of the tested covariates affected the PD parameters. Model-based simulations confirmed the concentration-dependent and non-cumulative properties of palbociclib-induced neutropenia, reversible after treatment withdrawal. The ANC nadir occurred approximately at day 24 of each cycle. Cox analyses revealed a trend for better PFS with increasing palbociclib exposure in older patients. By characterizing palbociclib-induced neutropenia, this model offers support to clinicians to rationally optimize treatment management through patient-individualized strategies.

Indexed as

neutropeniapalbociclibpharmacokineticsprogression-free survival

Identifiers

PMID35890213
PMCPMC9322950
OpenAlexW4283276894

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.