Prof. Dr. med. Frederik Marmé Sektionsleiter Translationale Gynäkologische Onkologie
Universitätsfrauenklinik und Nationales Centrum für Tumorerkrankungen
Heidelberg
Das metastasierte Mammakarzinom Highlights aus dem Jahr 2018
Dr. med. Julia Seitz
Universitätsfrauenklinik & Nationales Centrum für
Tumorerkrankungen Heidelberg
• AKT-Inhibitoren • PAKT • LOTUS
• PI3K – Inhibitoren
• SANDPIPER • SOLAR
• Antikörper-Drug Konjugat • Sacituzumab Govitecan
• PARP-Inhibitoren • OlympiAD
• Immuntherapie • Impassion 130
2018 Das Jahr der zielgerichteten Therapien
• AKT-Inhibitoren • PAKT • LOTUS
2018 Das Jahr der zielgerichteten Therapien
Schmid P et al., 2018 ASCO Annual Meeting oral session, abstract #
Randomized Phase II
N=140
mTNBC 1st Line
Prior taxan: 57%
• No biomarker preselection
• 1° EP: PFS
• 2° EP: PFS in PIK3CA/AKT1/PTEN altered tumors
80% power for
HR 0.67
1-sided alpha=10%
PAKT (Phase II) Paclitaxel +/- Capivasertib 1st line mTNBC
Schmid P et al., 2018 ASCO Annual Meeting oral session, abstract #
PAKT (Phase II) Paclitaxel +/- Capivasertib 1st line mTNBC
Schmid P et al., 2018 ASCO Annual Meeting oral session, abstract #
PAKT (Phase II) Paclitaxel +/- Capivasertib 1st line mTNBC
Dent R et al., 2018 ASCO Annual Meeting oral session, abstract #
Randomized Phase II
n=124
mTNBC 1st Line
Prior taxan: >50%
• No biomarker preselection
• co1° EP: PFS in IIT & TPENlow
• 2°: PIK3CA/AKT pathway activated population
LOTUS (Phase II) Paclitaxel +/- Ipatasertib 1st line mTNBC
Dent R et al., 2018 ASCO Annual Meeting oral session, abstract #
LOTUS (Phase II) Paclitaxel +/- Ipatasertib 1st line mTNBC
Dent R et al., 2018 ASCO Annual Meeting oral session, abstract #
LOTUS (Phase II) Paclitaxel +/- Ipatasertib 1st line mTNBC
• AKT-Inhibitoren • PAKT • LOTUS
• PI3K – Inhibitoren
• SANDPIPER • SOLAR
2018 Das Jahr der zielgerichteten Therapien
Baselga J et al.; ASCO 2018 MBC oral session LBA #1006
SANDPIPER (Phase III) Fulvestrant +/- TASELISIB in PIK3CAmt ER pos, Her2 neg mBC
Selektiver PI3K Inhibitor
(beta-sparing)
• N=516
• PIK3CA mutant (small wt cohort)
• 2:1 Rando
• Postmenopausal
• Progression on/after AI
• <5% prior CDK4/6
Baselga J et al.; ASCO 2018 MBC oral session LBA #1006
SANDPIPER (Phase III) Fulvestrant +/- TASELISIB in PIK3CAmt ER pos, Her2 neg mBC
Andre F, et al. ESMO 2018 (LBA3)
SOLAR-1 (Phase III) Fulvestrant +/- Alpelisib in PIK3CAmt HR pos, Her2 neg mBC
PI3K Inhibitor
Alpelisib
• N=572
• PIK3CA mutant (kleiner wt Kohorte)
• Postmenopausal
• Progression on/after AI
• Ca 6% prior CDK4/6
SOLAR-1 (Phase III) Fulvestrant +/- Alpelisib in PIK3CAmt HR pos, Her2 neg mBC
Juric D, et al. SABCS 2018 (GS3-08)
• AKT-Inhibitoren • PAKT • LOTUS
• PI3K – Inhibitoren
• SANDPIPER • SOLAR
• Antikörper-Drug Konjugat • Sacituzumab Govitecan
2018 Das Jahr der zielgerichteten Therapien
Bardia A et al., ASCO 2018 oral session MBC, abstract #
Antibody Drug Conjugates (ACD`s) Sacituzumab Govitecan
Bardia A et al., ASCO 2018 oral session MBC, abstract #
Antibody Drug Conjugates (ACD`s) Sacituzumab Govitecan
Phase I/II BASKET trial
HR+/HER2- Cohort
No preselection based on TROP-2 Expression
10mg/kg D1, 8 q3w
Tx bis PD oder Tox
Vortherapien: 69% CDK4/6i 54% mTORi Med. Linien: 5 (2-17) CHT: 2; ET: 3
Bardia A et al., ASCO 2018 oral session MBC, abstract #
Med. PFS 6.8 Mo (4.6 – 8.)
Antibody Drug Conjugates (ACD`s) Sacituzumab Govitecan
• AKT-Inhibitoren • PAKT • LOTUS
• PI3K – Inhibitoren
• SANDPIPER • SOLAR
• Antikörper-Drug Konjugat • Sacituzumab Govitecan
• PARP-Inhibitoren • OlympiAD
2018 Das Jahr der zielgerichteten Therapien
Robson ME et. al; J Clin Oncol 35, 2017 (suppl; abstr LBA4) – plenary session
• n= 302 • gBRCAmut
• 1st – 3rd Line • HR+: PD on ≥ 1L ET • standard CHT:
– capecitabine – eribulin – vinorelbine
• prim. EP: PFS(BICR)
• 50% TNBC • 50% ER+ • 28% prior
Platinum (PFI?) • 71% prior CHT
for MBC
OlympiAD (Phase III) Olaparib vs TPC mBC germline BRCAmut
Robson ME et. al; AACR 2018
OlympiAD (Phase III) Olaparib vs TPC mBC germline BRCAmut
• AKT-Inhibitoren • PAKT • LOTUS
• PI3K – Inhibitoren
• SANDPIPER • SOLAR
• Antikörper-Drug Konjugat • Sacituzumab Govitecan
• PARP-Inhibitoren • OlympiAD
• Immuntherapie • Impassion 130
2018 Das Jahr der zielgerichteten Therapien
IMpassion 130 (Phase III) Nab-Paclitaxel ± Atezolizumab 1st-line beim mTNBC
Schmid P, et al. ESMO 2018 (LBA1)
IMpassion 130 Update SABCS: Prädiktive Marker PD-L1 Status - PFS
Emens LA, et al. SABCS 2018 (GS1-04)
IMpassion 130 Update SABCS: Prädiktive Marker PD-L1 Status - PFS
Emens LA, et al. SABCS 2018 (GS1-04)
IMpassion 130 (Phase III) Nab-Paclitaxel ± Atezolizumab 1st-line beim mTNBC
Schmid P, et al. ESMO 2018 (LBA1)
IMpassion 130 (Phase III) Update SABCS
Emens LA, et al. SABCS 2018 (GS1-04)
Vielen Dank für die Aufmerksamkeit !