Evidence map›Paper›PMID 30151703›Full record

Trial reportJournal of neuro-oncology2018

Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma.

Jennie W Taylor, Mili Parikh, Joanna J Phillips, C David James, Annette M Molinaro, Nicholas A Butowski, Jennifer L Clarke, Nancy Ann Oberheim-Bush, Susan M Chang, Mitchel S Berger and 1 more

Open access · greenAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of neuro-oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 3 pooled it
7.1field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 3 syntheses or guidelines pooled it, 119 citations in OpenAlex.

  1. Guideline
  2. Pooled it
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  7. A Phase 0 Trial of Ribociclib in Recurrent Glioblastoma Patients Incorporating a Tumor Pharmacodynamic- and Pharmacokinetic-Guided Expansion Cohort.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Trial
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29 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 1 country.

Jennie W TaylorDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Mili ParikhDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Joanna J PhillipsDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
C David JamesDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Annette M MolinaroDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Nicholas A ButowskiDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Jennifer L ClarkeDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Nancy Ann Oberheim-BushDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Susan M ChangDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Mitchel S BergerDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Michael PradosDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. Michael.Prados@ucsf.edu.
Neurological Surgery · USUniversity of California, San Francisco · USNorthwestern University · US

Funding

Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Adult Brain Tumor Consortium (ABTC)U01CA137443 · NCI · JOHNS HOPKINS UNIVERSITY · PI GROSSMAN, STUART A, PRADOS, MICHAEL D · 2009 to 2013
$11.0M
NABTC - Foreign AccrualU01CA062399 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRADOS, MICHAEL D · 1994 to 2008
$4.7M
Cdk4/6 Inhibitor Therapy for Glioblastoma MultiformeR01CA159467 · NCI · GEORGETOWN UNIVERSITY · PI JAMES, CHARLES DAVID, WALDMAN, TODD A · 2012 to 2016
$1.6M
THERAPEUTIC STUDIES OF PRIMARY CNS MALIGNANCIESU01CA062422 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHANG, SUSAN M · 1994 to 2008
$1.3M
National Cancer Institute CA097257National Cancer Institute R01 CA159467NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA159467NCI NIH HHS U01 CA062399NCI NIH HHS U01 CA062422NCI NIH HHS U01 CA137443
6 · The paper itself

Abstract

introductionAlterations in the CDK4/6-RB signaling pathway are common causes of cell cycle dysregulation in many cancers, including glioblastoma. Palbociclib is an oral inhibitor of CDK4/6, which leads to phosphorylation of RB1 and cell-cycle arrest. We conducted a two-arm study evaluating efficacy and tissue pharmacokinetics/pharmacodynamics of palbociclib in patients with recurrent glioblastoma.

methodsEligibility criteria included confirmation of RB1 proficiency by IHC; ≤ 3 relapses; KPS ≥ 60; no limit on prior treatments. Arm 1 received palbociclib for 7 days prior to indicated resection followed by adjuvant palbociclib. Arm 2 received palbociclib without resection. Primary objective was PFS6; secondary included toxicity, OS, and ORR. Exploratory aims included biomarker assessment and pharmacokinetic/pharmacodynamic effects in surgical patients.

resultsTotal of 22 patients were enrolled; 6 on Arm 1 and 16 on Arm 2. Trial was stopped early secondary to lack of efficacy, with 95% of evaluable patients progressing within 6 months. Median PFS was 5.14 weeks (range 5 days-142 weeks) and median OS was 15.4 weeks (range 2-274 weeks). Two patients (10%) had related grade ≥ 3 AEs. In Arm 1, 5 patients had tissue concentrations of palbociclib felt to be sufficient for biological effect and paired samples available for RB1 IHC. There were no consistent changes in RB1 expression or cell proliferation in the paired tissue.

conclusionIn this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma. However, these were heavily pretreated patients and targeting the CDK4/6 pathway may still deserve further exploration.

Indexed as

AdultAgedAntineoplastic AgentsBiomarkers, TumorBrain NeoplasmsCombined Modality TherapyFemaleGlioblastomaHumansMaleMiddle AgedNeoplasm Recurrence, LocalPiperazinesPyridinesYoung AdultAntineoplastic AgentsBiomarkers, TumorpalbociclibPiperazinesPyridinesCDK4/6 inhibitorPalbociclibRecurrent glioblastomaRetinoblastoma pathway

Identifiers

PMID30151703
PMCPMC6239922
OpenAlexW2888948162

What OpenQuestion holds

Textmetadata
LicenceTDM
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.