Evidence map›Paper›PMID 31392595›Full record

Trial reportJournal of neuro-oncology2019

Phase I/II study of bevacizumab with BKM120, an oral PI3K inhibitor, in patients with refractory solid tumors (phase I) and relapsed/refractory glioblastoma (phase II).

John D Hainsworth, Kevin P Becker, Tarek Mekhail, Sajeel A Chowdhary, Janice Faulkner Eakle, David Wright, Robert M Langdon, Kathleen J Yost, Gilbert Darin Anthony Padula, Kimberly West-Osterfield and 5 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in Journal of neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 49 citations in OpenAlex.

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  14. Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024
    Review
  15. Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024
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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

15 authors at 5 institutions in 1 country.

John D HainsworthTennessee Oncology PLLC, 4220 Harding Road, Ste. 200, Nashville, TN, 37205, USA.
Kevin P BeckerYale University, New Haven, CT, USA.
Tarek MekhailFlorida Cancer Specialists/SCRI, Ft. Myers, FL, USA.
Sajeel A ChowdharyFlorida Cancer Specialists/SCRI, Ft. Myers, FL, USA.
Janice Faulkner EakleFlorida Cancer Specialists/SCRI, Ft. Myers, FL, USA.
David WrightFlorida Cancer Specialists/SCRI, Ft. Myers, FL, USA.
Robert M LangdonNebraska Methodist Cancer Center, Omaha, NE, USA.
Kathleen J YostGrand Rapids Oncology Program, Grand Rapids, MI, USA.
Gilbert Darin Anthony PadulaGrand Rapids Oncology Program, Grand Rapids, MI, USA.
Kimberly West-OsterfieldSarah Cannon, Nashville, TN, USA.
Meredith ScarberrySarah Cannon, Nashville, TN, USA.
Candice A ShaiferSarah Cannon, Nashville, TN, USA.
Mythili ShastrySarah Cannon, Nashville, TN, USA.
Howard A BurrisSarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN, USA.
Kent ShihSarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN, USA. kshih@tnonc.com.ORCID http://orcid.org/0000-0002-6718-6116
Sarah Cannon · USFlorida Cancer Specialists & Research Institute · USGrand Rapids Community College · USTennessee Oncology · USYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCurrent bevacizumab-based regimens have failed to improve survival in patients with recurrent glioblastoma. To improve treatment efficacy, we evaluated bevacizumab + BKM120, an oral pan-class I PI3K inhibitor, in this patient population.

methodsA brief phase I study established the optimal BKM120 dose to administer with standard-dose bevacizumab. BKM120 60 mg PO daily + bevacizumab 10 mg/kg IV every 2 weeks in 28-day cycles was then administered to patients with relapsed/refractory glioblastoma in the phase II portion.

resultsEighty-eight patients enrolled (phase I, 12; phase II, 76). In phase I, BKM120 80 mg PO daily produced dose limiting toxicity in 3 of 6 patients; a BKM120 dose of 60 mg PO daily was established as the maximum tolerated dose. In phase II, the median progression-free survival (PFS) was 4.0 months (95% CI 3.4, 5.4), PFS at 6 months was 36.5%, and the overall response rate was 26%. Forty-two patients (57%) experienced one or more serious treatment related toxicities. The most common CNS toxicities included mood alteration (17%) and confusion (12%); however, these were often difficult to classify as treatment- versus tumor-related.

conclusionsThe efficacy seen in this study is similar to the efficacy previously reported with single-agent bevacizumab. This regimen was poorly tolerated, despite the low daily dose of BKM120. Further development of this combination for the treatment of glioblastoma is not recommended.

Indexed as

Salvage TherapyAdultAgedAged, 80 and overAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBevacizumabDrug Resistance, NeoplasmFemaleFollow-Up StudiesGlioblastomaHumansMaleMaximum Tolerated DoseMiddle AgedMorpholinesAminopyridinesBevacizumabMorpholinesNVP-BKM120Phosphatidylinositol 3-KinasesBevacizumabBKM120Blood-brain barrierGlioblastomaPI3K pathway

Identifiers

PMID31392595
OpenAlexW2965915703

What OpenQuestion holds

Textmetadata
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.