Evidence map›Paper›PMID 28923573›Full record

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

Neoadjuvant buparlisib plus trastuzumab and paclitaxel for women with HER2+ primary breast cancer: A randomised, double-blind, placebo-controlled phase II trial (NeoPHOEBE).

Sibylle Loibl, Lorena de la Pena, Valentina Nekljudova, Dimitrios Zardavas, Stefan Michiels, Carsten Denkert, Mahdi Rezai, Begoña Bermejo, Michael Untch, Soo Chin Lee and 10 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
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. It is linked to trial NCT01816594 (NeoPHOEBE), which is not on this map. Cited by 57 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 5 pooled it
–field-weighted citation impact
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.

NCT01816594 phase2completednot on this map

NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer

TypeinterventionalSponsorNovartis PharmaceuticalsRan2013 to 2015Enrolled50ConditionsHER2-positive Newly Diagnosed, Primary Breast CancerArmsBKM120, Trastuzumab, Paclitaxel, BKM120 Placebo
3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 5 syntheses or guidelines pooled it.

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  3. The Predictive Role ofBioMed research international · 2020
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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

20 authors.

Sibylle LoiblGerman Breast Group, Neu-Isenburg, Germany; Sana-Klinikum Offenbach, Germany. Electronic address: Sibylle.Loibl@gbg.de.
Lorena de la PenaSOLTI Breast Cancer Research Group, Barcelona, Spain.
Valentina NekljudovaGerman Breast Group, Neu-Isenburg, Germany.
Dimitrios ZardavasBreast International Group, Brussels, Belgium.
Stefan MichielsGustave Roussy, Service de Biostatistique et d'Epidémiologie, Villejuif, France; CESP, Inserm U1018, Univ. Paris Sud, Univ. Paris-Saclay, Villejuif, France.
Carsten DenkertInstitute of Pathology, Charité University Hospital, Berlin, Germany.
Mahdi RezaiLuisenkrankenhaus Düsseldorf, Germany.
Begoña BermejoHospital Clinico Universitario de Valencia, Spain.
Michael UntchHelios Klinikum Berlin-Buch, Department of Obstetrics and Gynaecology, Berlin, Germany.
Soo Chin LeeDepartment of Haematology-Oncology, National University Cancer Institute, Singapore.
Sabine TurriNovartis Pharma SAS, Rueil Malmaison, France.
Patrick UrbanNovartis Pharma AG, Basel, Switzerland.
Sherko KümmelKliniken Essen-Mitte, Essen, Germany.
Guenther StegerDepartment of Internal Medicine I, Division of Oncology, Medical University of Vienna, Austria; Comprehensive Cancer Center Vienna, Austria.
Andrea GombosUniversité Libre de Bruxelles, Institut Jules Rue Héger-Bordet 1, Medical Oncology Clinic, Belgium.
Michael LuxUniversity Breast Centre of Franconia, OBGYN Department, University Hospital Erlangen, CCC Erlangen-EMN, Germany.
Martine J PiccartBreast International Group, Brussels, Belgium; Université Libre de Bruxelles, Institut Jules Rue Héger-Bordet 1, Medical Oncology Clinic, Belgium.
Gunter Von MinckwitzGerman Breast Group, Neu-Isenburg, Germany.
José BaselgaSOLTI Breast Cancer Research Group, Barcelona, Spain; Memorial Sloan-Kettering Cancer Center, New York, USA.
Sherene LoiPeter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Australian New Zealand Breast Cancer Trials Group (ANZBCTG), Newcastle, Australia. Electronic address: sherene.loi@petermac.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

aimThe Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer.

methodsNeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel. Primary end-point was pathological complete response (pCR) rate; key secondary end-point was objective response rate (ORR) at 6 weeks. Exploratory end-points were evaluation of Ki67 levels and change in tumour infiltrating lymphocytes (TILs) in intermediate biopsies at day 15.

resultsRecruitment was suspended mainly due to liver toxicity after enrolment of 50 of the planned 256 patients. In each arm (buparlisib n = 25; placebo n = 25) 21 patients (84%) had wild type PIK3CA and 4 patients (16%) had mutant PIK3CA. Overall, pCR rate was similar between buparlisib and placebo arms (32.0% versus 40%; one-sided P = 0.811). A trend towards higher ORR (68.8% versus 33.3%; P = 0.053) and a significant decrease in Ki67 (75% versus 26.7%; P = 0.021) was observed in buparlisib versus placebo arm in the ER+ subgroup (P

conclusionsAddition of the pan-PI3K inhibitor buparlisib to taxane-trastuzumab-based therapy in HER2+ early breast cancer was not feasible. However, the higher ORR and Ki67 reduction in the ER+, HER2+ subgroup indicates a potential role for PI3K-targeted therapy in this setting and may warrant further investigation with better-tolerated second-generation PI3K inhibitors. TRIAL REGISTRATION IDENTIFIER: NCT01816594.

Indexed as

Neoadjuvant TherapyAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsAustraliaBiomarkers, TumorBiopsyBreast NeoplasmsChemical and Drug Induced Liver InjuryChemotherapy, AdjuvantClass I Phosphatidylinositol 3-KinasesDouble-Blind MethodEarly Termination of Clinical TrialsErb-b2 Receptor Tyrosine KinasesEuropeAminopyridinesBiomarkers, TumorClass I Phosphatidylinositol 3-KinasesERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesKi-67 AntigenMorpholinesNVP-BKM120PaclitaxelPIK3CA protein, humanProtein Kinase InhibitorsTrastuzumabBuparlisibHER2NeoadjuvantNeoPHOEBEpCRPrimary breast cancer

Identifiers

PMID28923573
PMCPMC5640494

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Registered trials

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.