Evidence map›Paper›PMID 28502694›Full record

Trial reportEuropean journal of cancer (Oxford, England : 1990)2017

Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer.

Andrew J Armstrong, Susan Halabi, Patrick Healy, Joshi J Alumkal, Carolyn Winters, Julie Kephart, Rhonda L Bitting, Carey Hobbs, Colleen F Soleau, Tomasz M Beer and 4 more

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

Trial report in European journal of cancer (Oxford, England : 1990), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
9.2field-weighted citation impact, top 1% 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

54 citing papers in PubMed, 93 citations in OpenAlex.

  1. Phase Ib/II Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  2. Trial
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  5. Targeting the PI3K/AKT/mTOR signaling pathway in prostate cancer: Molecular dysregulation, therapeutic advances, and future directions.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
    Review
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  11. Article
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  14. Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023
    Review
  15. Article
  16. Reversal of Lactate and PD-1-mediated Macrophage Immunosuppression Controls Growth of PTEN/p53-deficient Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 1 country.

Andrew J ArmstrongDuke University Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Division of Medical Oncology, The Duke Cancer Institute, Durham, NC, USA. Electronic address: andrew.armstrong@duke.edu.
Susan HalabiDuke University Department of Biostatistics, USA.
Patrick HealyDuke University Department of Biostatistics, USA.
Joshi J AlumkalKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Carolyn WintersDuke University Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Division of Medical Oncology, The Duke Cancer Institute, Durham, NC, USA.
Julie KephartDuke University Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Division of Medical Oncology, The Duke Cancer Institute, Durham, NC, USA.
Rhonda L BittingWake Forest University, Winston-Salem, NC, USA.
Carey HobbsDuke University Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Division of Medical Oncology, The Duke Cancer Institute, Durham, NC, USA.
Colleen F SoleauUniversity of Washington, Seattle, WA, USA.
Tomasz M BeerKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Rachel SlottkeKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Kelly MundyDuke University Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Division of Medical Oncology, The Duke Cancer Institute, Durham, NC, USA.
Evan Y YuUniversity of Washington, Seattle, WA, USA.
Daniel J GeorgeDuke University Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Division of Medical Oncology, The Duke Cancer Institute, Durham, NC, USA.
Duke Cancer InstituteOregon Health & Science University · USDuke Medical Center · USDuke University · USUniversity of Washington · USWake Forest University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
NCI NIH HHS P30 CA014236
6 · The paper itself

Abstract

backgroundPhosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway activation is common in metastatic castration resistant prostate cancer (mCRPC). Buparlisib is an oral, pan-class I PI3 kinase inhibitor.

methodsThis was a multisite single arm phase II trial of buparlisib 100 mg ± enzalutamide daily in men with mCRPC whose disease progressed on or who were not candidates for docetaxel. The primary end-point was the rate of radiographic/clinical progression-free survival (PFS) at 6 months.

resultsThirty men were accrued: 67% post-docetaxel; median prostate specific antigen (PSA) was 70 ng/dl, 83% had ≥4 prior therapies for mCRPC; 43% received concurrent enzalutamide. The final 6 month PFS rate was estimated to be 10% (95% confidence interval 2.5-23.6%). Median PFS was 1.9 months and was 3.5 months with concurrent enzalutamide. Median overall survival was 10.6 months. Concurrent enzalutamide led to a five-fold reduction in buparlisib concentrations. PSA declines were observed in 23%; no patients achieved a ≥50% decline, and no radiographic responses were observed. Severe adverse events occurred in four men including respiratory infection and multi-organ failure, urinary tract obstruction, confusion and one seizure in the setting of a new central nervous system (CNS) metastasis. Grade III adverse events were seen in 43% of patients; common toxicities included grade I-II weight loss, diarrhoea, nausea, fatigue, anorexia, rash, hyperglycemia and anxiety/mood disorders.

conclusionsBuparlisib did not demonstrate significant activity in men with mCRPC, suggesting that PI3K inhibition is not sufficient to reverse resistant mCRPC progression. Future studies of PI3K pathway inhibitors with concurrent enzalutamide should develop optimal dosing and focus on selected patients more likely to benefit.

Indexed as

AgedAged, 80 and overAminopyridinesAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBenzamidesDisease-Free SurvivalHumansMaleMiddle AgedMorpholinesNitrilesPhenylthiohydantoinPhosphoinositide-3 Kinase InhibitorsProstatic Neoplasms, Castration-ResistantProtein Kinase InhibitorsAminopyridinesAntineoplastic AgentsBenzamidesenzalutamideMorpholinesNitrilesNVP-BKM120PhenylthiohydantoinPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsBKM-120BuparlisibClinical trialEnzalutamideMetastatic castration resistant prostate cancerPI3 kinaseProstate cancer

Identifiers

PMID28502694
PMCPMC6345641
OpenAlexW2613524609

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.