Das metastasierte Mammakarzinom - GBG...(beta-sparing) • N=516 • PIK3CA mutant (small wt cohort)...

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 !