(HER2-negative) locally advanced or metastatic breast cancer

(HER2-negative) locally advanced or metastatic breast cancer

A phase II trial of Abiraterone acetate plus prednisone in patients with molecular
apocrine (HER2-negative) locally advanced or metastatic breast cancer: a UCBG study
410TiP
A. Gonçalves1, A. Mailliez2, F. Dalenc3, B. You4, T. L’haridon5, M. Leheurteur6, O. Tredan7, J.-M. Ferrero8, F. Del Piano9, C. Alliot10, B. Lucas11, N. Dohollou12, P.H. Cottu13, J. Dauba14, P. De Cremoux15, J.-Y. Pierga13, C. Orsini16,
M. Pulido17, G. Macgrogan17, H. Bonnefoi17;
1INSTITUT PAOLI CALMETTES Marseille/FR, 2CENTRE OSCAR LAMBRET Lille/FR, 3INSTITUT CLAUDIUS REGAUD Toulouse/FR, 4CH LYON SUD Lyon/FR, 5CHD DE VENDEE La Roche-sur-yon/FR, 6CENTRE HENRI BECQUEREL Rouen/FR, 7CENTRE LEON BERARD Lyon/FR, 8
CENTRE ANTOINE LACASSAGNE Nice/FR, 9HOPITAUX DU LEMAN Thonon Les Bains/FR, 10 CH ALPES LEMAN Contamine-Sur-Arve/FR, 11 CHU DE BREST-HÔPITAL MORVAN Brest/FR, 12 POLYCLINIQUE BORDEAUX NORD AQUITAINE Bordeaux/FR, 13 INSTITUT CURIE
Paris/FR, 14 CH DE MONT DE MARSAN Mont-de-Marsan/FR, 15 Hôpital Saint Louis-Université Paris-Diderot Paris/FR, 16UNICANCER Paris/FR, 17INSTITUT BERGONIE Bordeaux/FR
BACKGROUND
The molecular apocrine breast cancer subset has recently been identified. These tumours
are estrogen receptor (ER) negative but are characterised by the expression of many
genes expressed by ER-positive luminal tumours and, interestingly, are androgen receptor
(AR) positive. One third of these tumours are HER2-negative.
Abiraterone acetate (AA) is a novel, selective, irreversible, and potent inhibitor of CYP17
enzymatic activity that reduces testosterone levels in the blood to undetectable range.
We embarked on this phase II to explore the efficacy and savety of abiraterone in patients
with molecular apocrine (HER2-negative) locally advanced or metastatic breast cancer.
ELIGIBILITY
STUDY ACCRUAL (August 2014)
INCLUSION CRITERIA:
 Women aged ≥ 18 years;
 Histologically confirmed locally advanced or metastatic breast cancer;
 Molecular apocrine cancer
ER- , PR- (IHC ≤ 10%)*
AR+ ( IHC >10%)
 HER2-negative
 Chemotherapy-naive or previously treated by chemotherapy (if life expectancy ≥ 3 months)
 Measurable or non measurable disease according to RECIST v1.1 criteria;
SCREENING (N=108)
SCREENING - > INCLUSION (N=25)
Histological Type
(Central Review)
ER-; PR-; HER2-; AR+
* In case of discordant ER and/or PR status between the primary tumour and the metastatic site, the
status of the metastatic site will be used to decide whether the patient would be eligible or not.
(N=108)
37 (34%) -> eligible
ER-; PR-; HER2-;
AR-
53 (49%)
ER-; PR-; HER2+;
AR-
1 (1%)
ER+; PR-; HER2-;
AR-
4 (4%)
ER+; PR-; HER2-;
AR+
4 (4%)
ER+; PR+; HER2-;
AR+
Incluable Patients
after central Review
(N=37)
enrolled
25 (68%)
Ongoing inclusion
6 (16%)
No more eligible
6 (16%)
Reason for non inclusion
after screening (ER-; PR-; HER2-; AR+)
2
Exclusion Criteria
2 (2%)
2
Patient Deaths
Not done
5 (5%)
1
Investigator Decision
Ongoing
2 (2%)
1
Patient Decision
STUDY DESIGN
OBJECTIVES
PRIMARY OBJECTIVE:
To estimate antitumour activity of abiraterone acetate, as measured by the 6-months
clinical benefit rate (CBR) in molecular apocrine HER2-negative locally advanced or
metastatic breast cancer.
SECONDARY OBJECTIVES:
 Objective response rate (ORR)
 Duration of overall response (DoR)
 Overall survival (OS)
 Progression-free survival (PFS)
 Tolerance and safety of abiraterone acetate.
Treatment
Period
Post-Treatment
Period
Follow-up
Period
Cn
2 years
W1 W2 W3 W4 W1 W2 W3 W4
D-28
D1
Cycle 1
Cycle 2
CONCLUSION
Abiraterone 1000mg/day
Prednisone 10mg/day
W = Week
D = Day
The study accrual is good and the target accrual will be achieved earlier than planned
The number of patients screened is lower than anticipated, probably because the
investigators made a pre-sreening with local AR evaluation
= Centralized review of tumour status (AR+, ER-, PR- and HER2-)
= CT scan and/or MRI
A following trial is under preparation.
TRANSLATIONAL RESEARCH
 To identify biomarkers of response to Abiraterone acetate using tumour tissue samples (from the
primary tumour or from metastatic sites) and blood and serum samples. Translational research
studies will include IHC, metabolomics, proteomics, pharmacogenetic and pharmacodynamic
(tumour biomarkers, blood endocrine profile).
 To improve molecular definition of apn breast cancer (RT-qPCR, gene expression profiling, NGS)
 To describe the variation of CTC (Circulating Tumour Cells) levels and to evaluate the predictive
value of the variation of CTC levels on the objective response rate, the clinical benefice rate and
survival.
[email protected]
[email protected]
LIST OF PRINCIPAL INVESTIGATORS
METHODOLOGY:
Uncontrolled,
open-label,
multicentric, phase II study
prospective,
Number of patients : 31 patients
Inclusion Period : 24 months
Treatment Period : Until progression or
unacceptable toxicity
Follow-up period : 24 months
Docteur Julien GRENIER
ORLEANS
PARIS
CHR D ORLEANS - HOPITAL LA SOURCE
HÔPITAL TENON
Docteur Corina CORNILA-PREDA
Docteur Joseph GLIGOROV
Docteur Christian VILLANUEVA
PARIS
HÔPITAL SAINT-LOUIS
Docteur Marc ESPIÉ
PARIS
INSTITUT CURIE - HÔPITAL CLAUDIUS REGAUD
Docteur Paul COTTU
PERPIGNAN
CH DE PERPIGNAN
Docteur Fawzi KARA SLIMANE
Docteur Brigitte LUCAS
PIERRE BENITE
CH LYON SUD
Docteur Benoit YOU
CH DE LA REGION D'ANNECY
Docteur Laetitia STEFANI
Primary objective:
Clinical benefit (RC + RP + SD ≥ 24 weeks)
ANGERS
ICO - SITE PAUL PAPIN
Docteur Sophie ABADIE-LACOURTOISIE
AVIGNON
INSTITUT SAINTE CATHERINE
BESANCON
CHU - HOPITAL JEAN MINJOZ
BORDEAUX
INSTITUT BERGONIE
Professeur Hervé BONNEFOI
Statistical analysis
Single stage design
H0: Baseline clinical benefit rate 15%
Target clinical benefit rate 35%
Power 80%
Alpha 5%
N=31 (including 10% NE)
BORDEAUX Cedex
POLYCLINIQUE BORDEAUX NORD AQUITAINE
Docteur Nadine DOHOLLOU
BREST
CHU DE BREST - HÔPITAL MORVAN
CAEN
CENTRE FRANCOIS BACLESSE
Docteur Christelle LEVY
PRINGY
CLERMONT-FERRAND
CONTAMINE - SUR - ARVE
DIJON
CENTRE JEAN PERRIN
CH ALPES LEMAN
CENTRE GEORGES-FRANÇOIS LECLERC
Docteur Marie-Ange MOURET-REYNIER
Docteur Carol ALLIOT
Docteur Isabelle DESMOULINS
REIMS
INSTITUT JEAN GODINOT
Docteur Christelle JOUANNAUD
ROUEN
CENTRE HENRI BECQUEREL
Docteur Marianne LEHEURTEUR
SAINT-CLOUD
INSTITUT CURIE - HÔPITAL RENÉ HUGUENIN
Docteur Coraline DUBOT
GRENOBLE
CHU DE GRENOBLE - HOPITAL MICHALLON
Professeur Mireille MOUSSEAU
SAINT-HERBLAIN
ICO- SITE RENE GAUDUCHEAU
Docteur Mario CAMPONE
HYERES
CLINIQUE SAINTE MARGUERITE
Docteur Jean-François BERDAH
STRASBOURG
CENTRE PAUL STRAUSS
Professeur Thierry PETIT
LA ROCHE-SUR-YON
CHD DE VENDEE
Docteur Véronique GIRRE
STRASBOURG
HOPITAL CIVIL - STRASBOURG
Docteur Philippe BARTHELEMY
LILLE
CENTRE OSCAR LAMBRET
Docteur Audrey MAILLIEZ
THONON LES BAINS
HOPITAUX DU LEMAN
Docteur Francesco DEL PIANO
LYON
CENTRE LEON BERARD
Docteur Olivier TREDAN
TOULOUSE
INSTITUT CLAUDIUS REGAUD
Docteur Florence DALENC
MARSEILLE
INSTITUT PAOLI CALMETTES
Docteur Anthony GONCALVES
VANNES
CH BRETAGNE ATLANTIQUE
Docteur Emmanuel BLOT
MONT DE MARSAN
CH DE MONT DE MARSAN
Docteur Jérôme DAUBA
NICE
CENTRE ANTOINE LACASSAGNE
Professeur Jean-Marc FERRERO
VANNES
VILLEJUIF
HÔPITAL PRIVÉ OCÉANE
GUSTAVE ROUSSY CANCER CAMPUS
Docteur Emmanuel BLOT
Docteur Mahasti SAGHATCHIAN
With the grant support of Janssen-Cilag