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 !