Evidence map›Paper›PMID 29198055›Full record

Trial reportBreast cancer research and treatment2018

Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.

B Pistilli, T Pluard, A Urruticoechea, D Farci, A Kong, T Bachelot, S Chan, H S Han, G Jerusalem, P Urban and 5 more

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

Trial report in Breast cancer research and treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Review
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  7. Review
  8. Article
  9. Review
  10. Review
  11. Role of EGFR and FASN in breast cancer progression.Journal of cell communication and signaling · 2023
    Review
  12. Review
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  14. Review
  15. Review
  16. Article
  17. Therapeutic landscape of advanced HER2-positive breast cancer in 2022.Medical oncology (Northwood, London, England) · 2022
    Review
  18. An Insight into Molecular Targets of Breast Cancer Brain Metastasis.International journal of molecular sciences · 2022
    Review
  19. Leptomeningeal Metastases: New Opportunities in the Modern Era.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  20. Review
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 12 institutions in 7 countries.

B PistilliBreast Cancer Unit, Institut Gustave Roussy, 114 Rue Edouard-Vaillant, 94800, Villejuif, France. barbara.pistilli@gustaveroussy.fr.ORCID http://orcid.org/0000-0002-9184-7199
T PluardSaint Luke's Health System, Kansas City, MO, USA.
A UrruticoecheaOnkologikoa Foundation, San Sebastian, Spain.
D FarciOspedale Oncologico, Cagliari, Italy.
A KongUniversity of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
T BachelotCentre Léon Bérard et Inserm U1052, Lyon, France.
S ChanNottingham University Hospitals NHS Trust, Nottingham, UK.
H S HanMoffitt Cancer Center, Tampa, FL, USA.
G JerusalemCHU Sart Tilman Liège and University of Liège, Liège, Belgium.
P UrbanNovartis Pharma AG, Basel, Switzerland.
D RobinsonNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
S L MouhaërNovartis Pharmaceuticals Corporation, Rueil-Malmaison, France.
E D TomasoNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
C MassacesiNovartis Pharmaceuticals Corporation, Rueil-Malmaison, France.
C SauraVall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Novartis (France) · FRNovartis (United States) · USInserm · FRInstitut Català d'Ornitologia · ESInstitut Gustave Roussy · FRMoffitt Cancer Center · USNottingham University Hospitals NHS Trust · GBNovartis (Switzerland) · CHSaint Luke's Health System · USUniversity Hospitals Birmingham NHS Foundation Trust · GBUniversity of Liège · BEVall d'Hebron Hospital Universitari · ES

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
NCI NIH HHS P30 CA076292
6 · The paper itself

Abstract

purposeA Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion.

methodsPatients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab. Study endpoints included safety/tolerability and antitumour activity. The study was extended to include a Phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine.

resultsIn the Phase II portion, of 50 patients treated with buparlisib and trastuzumab, the most common (≥ 30%) all-grade adverse events (AEs) were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved complete response and four (8%) patients had confirmed partial responses [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint (ORR ≥ 25%) was therefore not met. In the Phase Ib portion, all patients with measurable brain lesions at baseline showed tumour shrinkage to some degree; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined.

conclusionBuparlisib plus trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety profile but limited efficacy in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine.

Indexed as

AdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBrain NeoplasmsBreast NeoplasmsCapecitabineDisease ProgressionDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleHumansMaximum Tolerated DoseMiddle AgedMorpholinesAminopyridinesBiomarkers, TumorCapecitabineERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesMorpholinesNVP-BKM120TrastuzumabAdvanced/metastatic breast cancerBrain metastasesBuparlisibHER2-positiveHerceptinTrastuzumab pretreated

Identifiers

PMID29198055
PMCPMC7771343
OpenAlexW2771347254

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.