das metastasierte mammakarzinom - gbg...(beta-sparing) • n=516 • pik3ca mutant (small wt cohort)...
TRANSCRIPT
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 !