Decision impact Studien

Decision Impact Studien
BCIST und PRIMe
und
PROTROCA
Dr. med. Rachel Würstlein, LMU München
WSG plus MSG
2
BCIST und PRIME
Decision impact Studien beim Einsatz von Genexpressionsanalysen in der
adjuvanten Therapie bei HR pos Mammakarzinom
3
Strategie frühes Mammakarzinom
ER and/or PR positive
(HER2 negative)
Lymph node involvement (< 3 vs > 4 LK)
Grade
Tumor biology
• uPA/PAI-1
• Gene-signatures
• Ki-67
Low risk
endocrine
therapy
High risk
chemotherapy
→ endocrine
therapy
adapted from Harbeck, Salem, Gluz et al, 2010
4
March 18, 2015
Chemotherapy yes or no?
Ki-67
uPA/PAI-1
Multigene tests:
Oncotype DX: plan B, ADAPT
Endopredict
Mammaprint: PRIME
PAM50: BCIST
5
6
7
8
9
Breast Cancer Intrinsic Subtype Test
BCIST:
Einsatz von Prosigna
10
Development of the Prosigna® test:
PAM50 gene signature
2000
2009
2010
2012/13
Researchers first describe breast
cancer intrinsic subtypes based on
microarray experiments
Researchers first describe
“PAM50” gene expression
signature
NanoString exclusively licenses
PAM50 gene expression signature
Prosigna launches after
receiving CE Mark for
Europe & Israel; FDA
510k clearance in US
PAM50 developed by a consortium of four academic breast
cancer experts
Charles Perou, PhD, University of North Carolina
Dr. Matt Ellis, Washington University School of Medicine
Torsten Nielsen, MD, PhD, Pathologist, BC Cancer Agency
Source: Molecular portraits of breast cancer. Nature. 2000 May 25;.
Source: Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes, JCO.2009
11 March 18, 2015
Philip Bernard, MD, University of Utah / Huntsman Cancer Institute
Prosigna® patient report:
Intrinsic Subtype
– The only commercial PAM50-based
signature that identifies Luminal A,
Luminal B, Basal-like, and HER2enriched subtypes
Prosigna Score (ROR)
– Risk of recurrence based on the tumor
size, molecular intrinsic subtype,
proliferation status of the tumor, and
nodal status
Risk Category
– Specific to patient’s nodal status
Validation set of > 2400 postmenopausal
women with early-stage breast cancer
(ABCSG8, TransATAC)
Source: Prosigna Package Insert
KLINIKUM DER UNIVERSITÄT MÜNCHEN®
12 March 18, 2015
Brustzentrum
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
Decision impact Studien (EU)
Frankreich (ongoing)
Deutschland
Spanien
March 18, 2015
13
WSG BCIST Decision impact study
March 18, 2015
WSG GmbH
14
© Prof. Karl Sotlar, Munich
WSG BCIST Decision impact study
Prospective Observational Study of Clinical
Outcomes for NanoString Technologies Breast
Cancer Intrinsic Subtype Test
Multicenter prospective assessment of change in
cancer-specific clinical decisions and outcomes
before and after physicians received NanoString
BCIST results.
11 centers in Germany
N=198
Recruitment period: September 2013 – January 2015
March 18, 2015
WSG GmbH
15
Endpoints
Influence ot Prosigna gene signature assay results
on physicians adjuvant treatment recommendations
by determinint the extent of change in pre-test
treatment rcommendations following assay results.
Physicians and patiens confidence
Inter-observer variability
16
NanoString – Prosigna™ Decision Impact Study:
Final recruitment (October 20, 2014, n= 201)
18
19
Ergebnisse
Low to intermediate risk population
29,3% dixcordance in intrinsic subtypint with local immunohistochemistry test
results
Change in therapy recommendation: 36 pat ( 18,2%)
Switch to chemotherapy in 22 (11,1%) patients
increased confidence in their prognostic assessment in 87.9% of patients, and
increased confidence in their treatment recommendation in 89.4%.
Patients reported improved anxiety and emotional/functional well-being after
receiving Prosigna test results
No difference in molecular subtyping
No difference in risk assessment
Luminal A: 63,1%
Luminal B: 35,8%
Low-risk: 42,9%; High-risk: 21,7%
Intermediate risk: 35,4%
March 18, 2015
WSG GmbH
20
courtesy of Prof. Karl Sotlar, Munich
452 Pat. eingeschlossen (430 haben primären
Endpunkt erreicht + 22 Screening failures)
27 Zentren waren aktiv:
3 in Schweiz
1 in Österreich
23 in Deutschland
Die High Recruiter der PRIMe-Studie waren:
40 Patientinnen: Tübingen, Prof. Dr. Grischke
40 Patientinnen: München
35 Patientinnen: Kiel, PD Dr. Schem
Eingereicht als Poster für San Antonio
Publikation geplant
30
PROTROCA
PROTROCA Non-Interventional Study (NIS)
Prophylaxis of neutropenia in breast cancer with Lipegfilgrastim (Lonquex®)
Lonquex® (Lipegfilgrastim) , Langwirksamer G-CSF mit GlykoPEGylierung
Lonquex® Anwendungsgebiete:
Zur Verkürzung der Dauer von Neutropenien und zur Verminderung
der Inzidenz von febriler Neutropenie bei erwachsenen Patienten,
die wegen einer malignen Erkrankung eine zytotoxische Chemotherapie
erhalten (mit Ausnahme von chronisch-myeloischer Leukämie und
myelodysplastischen Syndromen).
31
32
33
34
35
36
Geplant n= 550
Best-Rekrutierung:
LMU
Praxishetzwerk Troisdorf
Niels-Stensen-Kliniken
Franziskus-Hospital Harderberg
Georgsmarienhütte
Klinikum Deggendorf
MVZ Nordhausen
Gyn. Onk. Schwerpunktpraxis Hannover
Ansprechpartner:
Frau Meschenmoser (Projektleitung)
Trial Manager
WSG: Prof. Nitz, Prof. Harbeck
Dr. Würstlein
37
Wir wünschen einen schönen WSG-Abend
Danke für Ihre Aufmerksamkeit
38