Johannes EttlInterdisziplinäres Brustzentrum und Frauenklinik rechts der Isar,Technische Universität München Direktorin: Prof Dr M Kiechle
ASCO 2017: Highlights zur Therapie des t t i t M k i
Technische Universität München, Direktorin: Prof. Dr. M. Kiechle
PG Mamma, 20. Juli 2017
metastasierten Mammakarzinoms
ÜberblickÜberblick• PARP‐Inhibitoren beim BRCApos MBCA• PARP‐Inhibitoren beim BRCApos MBCA
– Talazoparib fortgeschrittene Linie: • #1007: Erste Phase II‐DAten
– Talazoparib fortgeschrittene Linie: • #1007: Erste Phase II‐DAten
– Olaparib 1st line: • #1000: Monarch 2
– Olaparib 1st line: • #1000: Monarch 2• #1000: Monarch 2
• PD1‐AK beim mTNBC• #1000: Monarch 2
• PD1‐AK beim mTNBC– Pembrolizumab
• #1008: Phase II Monotherapie– Pembrolizumab
• #1008: Phase II Monotherapie• CDK4/6‐Inhibitoren beim MBCA
– Palbociclib 1st line:• CDK4/6‐Inhibitoren beim MBCA
– Palbociclib 1st line:Palbociclib 1st line: • #1001: Finale OAS‐Ergebnisse PALOMA‐1
Abemaciclib 2nd line:
Palbociclib 1st line: • #1001: Finale OAS‐Ergebnisse PALOMA‐1
Abemaciclib 2nd line:– Abemaciclib 2nd line: • #1000: Monarch 2
– Abemaciclib 2nd line: • #1000: Monarch 2
PARP-Inhibitoren in klinischer Prüfung gbeim MBCA
Firma Verabreichung Dosierung Phase
Veliparib Abbvie p o 400 mg 1‐0‐1 I II IIIVeliparibABT‐888
Abbvie p.o. 400 mg 1‐0‐1 I,II,III
Ol ib A t Z 400 1 0 1 I II IIIOlaparibAZD2881
AstraZeneca p.o. 400 mg 1‐0‐1 I,II,III
RucaparibAGO14699
Clovis Oncology p.o. 600 mg 1‐0‐1 II
NiraparibMK‐4827
Tesaro p.o. 300 mg 1‐0‐1 I,II,III
TalazoparibBMN 673
Medivation(Biomarin)
p.o. 1 mg 1‐00 I,II,III
Final Results of a Phase 2 Study of Talazoparib (TALA) Following Platinum or Multiple Cytotoxic Regimens in Advanced Breast Cancer Patients (pts) With Germline BRCA1/2 Mutations (ABRAZO)
Presented By Nicholas Turner at 2017 ASCO Annual Meeting
ABRAZO (Phase II): Talazoparib nach Platin oder multipler CT beim gBRCA+ ABC(N=84) – Baseline Characteristics( )
Turner NC, et al. ASCO 2017 (abs 1007)
ABRAZO (Phase II): Talazoparib nach Platin oder multipler CT beim gBRCA+ ABC(N=84) – ORR, PFS, OS( ) , ,
ORR 21% ORR 37%ORR 21%PFS 4,0 MoOS 12,7 Mo
ORR 37%PFS 5,6 MoOS 14,7 Mo
Turner NC, et al. ASCO 2017 (abs 1007)
ABRAZO (Phase II): Talazoparib nach Platin oder multipler CT beim gBRCA+ ABC(N=84) – AEs( )
Turner NC, et al. ASCO 2017 (abs 1007)
Safety – Nonhematologic
Cohort 1Prior Platinum
Cohort 23L+, No Prior Platinum
(n = 48) (n = 35)All Grade Grade 3 Grade 4 All Grade Grade 3 Grade 4
Number of patients ≥ 1 TEAE, % (No.) 97.9 (47) 22.9 (11) 4.2 (2) 97.1 (34) 28.6 (10) 2.9 (1)
Fatigue 60.4 (29) 6.3 (3) 0 22.9 (8) 0 0g ( ) ( ) ( )
Nausea 41.7 (20) 4.2 (2) 0 42.9 (15) 0 0
Diarrhea 35.4 (17) 2.1 (1) 0 28.6 (10) 0 0
Decreased appetite 22.9 (11) 2.1 (1) 0 25.7 (9) 0 0
Dyspnea 22.9 (11) 2.1 (1) 2.1 (1) 25.7 (9) 5.7 (2) 0
Alopecia (grade 1) 22 9 (11) 0 0 20 0 (7) 0 0Alopecia (grade 1) 22.9 (11) 0 0 20.0 (7) 0 0
Back pain 22.9 (11) 0 0 20.0 (7) 0 0
Vomiting 20.8 (10) 0 0 20.0 (7) 0 0g ( ) ( )
Pleural effusion 8.3 (4) 6.3 (3) 0 11.4 (4) 5.7 (2) 0No grade 5 TEAEs were observed; no clinically significant cardiovascular toxicity.All TEAEs in ≥ 20% of patients and grade 3+ TEAEs in ≥ 5% of patients.p g p
8Presented by: Nicholas C. Turner
ABRAZO (Phase II): Talazoparib nach Platin oder multipler CT beim gBRCA+ ABC(N=84) – Conclusions( )
Turner NC, et al. ASCO 2017 (abs 1007)
OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients with HER2-negative metastatic breast cancer and a germline BRCA mutation
Presented By Mark Robson at 2017 ASCO Annual Meeting
OlympiAD study design
Presented By Mark Robson at 2017 ASCO Annual Meeting
Patient disposition
Presented By Mark Robson at 2017 ASCO Annual Meeting
Objective response by BICR
Presented By Mark Robson at 2017 ASCO Annual Meeting
Primary endpoint: progression-free survival by BICR
Presented By Mark Robson at 2017 ASCO Annual Meeting
Grade ≥3 adverse events in ≥2% patients in either arm
Presented By Mark Robson at 2017 ASCO Annual Meeting
Time to deterioration of global HRQoL
Presented By Mark Robson at 2017 ASCO Annual Meeting
Slide 1
Presented By Sylvia Adams at 2017 ASCO Annual Meeting
Slide 4
Presented By Sylvia Adams at 2017 ASCO Annual Meeting
Best Overall Response <br />(RECIST v1.1, Central Review)
Presented By Sylvia Adams at 2017 ASCO Annual Meeting
Overall Survival Results From the Randomized Phase 2 Study of Palbociclib in Combination With Letrozole vs Letrozole Alone for First-Line Treatment of ER+/HER2‒ Advanced Breast Cancer (PALOMA-1; TRIO-18)
Finn RS, et al. ASCO 2017 (abs 1001)
PALOMA-1: Phase 2 Study Design1
Finn RS, et al. ASCO 2017 (abs 1001)
Slide 9
Finn RS, et al. ASCO 2017 (abs 1001)
OS: Phase 2 (ITT)
Finn RS, et al. ASCO 2017 (abs 1001)
Time to Chemotherapy From Randomization
Finn RS, et al. ASCO 2017 (abs 1001))
Slide 1
Sledge GW, et al. ASCO 2017 (abs 1000)
Study Design
Sledge GW, et al. ASCO 2017 (abs 1000)
Primary Endpoint: PFS (ITT)
Sledge GW, et al. ASCO 2017 (abs 1000)
Slide 7
Sledge GW, et al. ASCO 2017 (abs 1000)
TEAE (Safety Population)
Sledge GW, et al. ASCO 2017 (abs 1000)
Grade 2 and 3 Diarrhea Pre- and Post-Dose Amendment
Sledge GW, et al. ASCO 2017 (abs 1000)
Summary of Exposure and Adverse Events
Sledge GW, et al. ASCO 2017 (abs 1000)
Take HomeTake Home
• Olaparib und Talazoparib als MONO‐Th i i k !Therapien wirksam!
• Pembrolizumab: Geduld, GeduldPembrolizumab: Geduld, Geduld• Palbociclib verlängert die Zeit bis zur ersten CTX
• Abemaciclib als dritter CDK4/6 Inhibitor• Abemaciclib als dritter CDK4/6‐Inhibitor wirksam
