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POETIC-APeri-Operative Endocrine Therapy for Individualised Care with Abemaciclib
Professor Stephen JohnstonProfessor Judith BlissProfessor Mitch Dowsett
Dr Alistair Ring
UK IBCS Birmingham, 27-28 January 2020
2
POETIC – successful delivery of complex trial
• Trial entry: Choice of patient pathways - flexible, pragmatic approach (Trials,2015)
• Pioneering PPI: recognised by NIHR & as exemplar (Clin Oncol, 2015 editorial)
130 UK centres
> 16,000 blood & >10,000 tumour samples collected
2000 staff atparticipating centres
4486 patients (>110 pts/mth at peak)
• Primary analysis presented by Robertson et al., SABCS 2017
POETIC
Baseline
2-week
Tumour - FFPE
100
75
50
25
0
% s
urv
ivin
g T
TR
event fr
ee
0 1 2 3 4 5Time post randomization (years)
3
H, L
H, H
100
75
50
25
0
% s
urv
ivin
g T
TR
event fr
ee
0 1 2 3 4 5Time post randomization (years)
L, L
Time To Recurrence (TTR) by baseline and 2-week Ki67 – Peri-op AI
100
75
50
25
0
% s
urv
ivin
g T
TR
event fr
ee
0 1 2 3 4 5Time post randomization (years)
In patients with Ki67B≥10%:
HR for Ki672W≥10% is 2.22 (95%CI: 1.68, 2.94; p<0.001)
Ki67B Ki672W TTR events/Total
5 year absolute risk,
% (95%CI)
L L 31 / 743 4.5 (3.1, 6.6)
H L 101 / 1202 8.9 (7.2, 11.0)
H H 96 / 551 19.6 (15.9, 24.1)
Robertson et al., SABCS 2017
100
75
50
25
0
% s
urv
ivin
g T
TR
event fr
ee
0 1 2 3 4 5Time post randomization (years)
4
H, L
H, H
100
75
50
25
0
% s
urv
ivin
g T
TR
event fr
ee
0 1 2 3 4 5Time post randomization (years)
L, L
Time To Recurrence (TTR) by baseline and 2-week Ki67 – Peri-op AI
100
75
50
25
0
% s
urv
ivin
g T
TR
event fr
ee
0 1 2 3 4 5Time post randomization (years)
Ki67B Ki672W TTR events/Total
5 year absolute risk,
% (95%CI)
L L 31 / 743 4.5 (3.1, 6.6)
H L 101 / 1202 8.9 (7.2, 11.0)
H H 96 / 551 19.6 (15.9, 24.1)
Robertson et al., SABCS 2017
Identify High
risk
target
population
5
N=5600*
Histologically Confirmed HR+ HER2-
Pre- post menopausal women w/ Stage III or Stage IIB Or Stage 2A*
No more than 12 mos since initial pathologic diagnosis
Prior chemo allowed
Arm A
Palbociclib (2
yrs)
+
ET (5-10 yrs)
Arm B
ET (5-10 yrs)
R
A
N
D
O
M
I
Z
A
T
I
O
N
1:1
Primary End Point: • iDFS (Invasive Disease Free Survival)
Secondary End Points:
• iDFS excluding secondary primary non-BC,
• OS, PROs, Safety
HR+,
HER2-,
Node+,
high-
risk,
early-
stage
breast
cancer
Long-term Follow-up
Period
On-Study
Treatment
Period
6-10 years3-5 years2 years
ARM A:
Standard
Endocrine
Therapy
(SOC) +
Abemaciclib
(150mg BID)
ARM B:
Standard
Endocrine
Therapy
(SOC) Alone
~4580 patients
1:1 randomization
PALLAS NCT02513394 (available from https://clinicaltrials.gov/ct2/show/NCT02513394)
MONARCH-E NCT03155997 (available from https://clinicaltrials.gov/ct2/show/NCT03155997
Phase III trials of adjuvant CDK 4/6 inhibitors in early breast cancer
PALLAS MONARCH-E
Presentation with Primary Breast Cancer
ER+ and HER2- andKi67>/= 20%
2 weeks’ AI
ER- orHER2+ or
Ki67 <20%ineligible
Ki67 < 8% ineligible
Ki67 >/= 8%
Complete standard of care treatment
Diagnostic biopsy
Clinical end-point: TTRHRs: 0.5 for profile +ve
0.9 for profile -ve
Core-cut at surgery
AIR-CIS positiveRANDOMISE
AIR-CIS negativeRANDOMISE
ET only ET onlyET + abemaciclib
ET + abemaciclib
POETIC-A Pre-Operative Endocrine Therapy for Individualised Care withAbemaciclib
Design: Prospective, multi‐centre, randomised, phase III
Primary Aim: To determine whether a molecular algorithm (AIR-CIS) can identify those postmenopausalwomen with ER+ HER2- primary breast cancer and poor antiproliferative response to an aromatase inhibitor(AI) who may derive greatest benefit from additional adjuvant endocrine therapy with abemaciclib.
Key Eligibility Criteria for registration:• ER+, HER2-• Postmenopausal• Palpable tumour of any size or ≥1.5cm by imaging
• Baseline Ki67 ≥ 20% measured at the local siteOR
• Presence of clinico-pathologic factors that predict (>50% chance) patients with Ki67 ≥ 8% after 2weeks’ AI:• grade 3• clinical/radiological tumour size > 5cm• PgR negative or PgR unknown AND evidence of vascular invasion.
POETIC-A Pre-Operative Endocrine Therapy for Individualised Care withAbemaciclib
Design: Prospective, multi‐centre, randomised, phase III
Primary Aim: To determine whether a molecular algorithm (AIR-CIS) can identify those postmenopausalwomen with ER+ HER2- primary breast cancer and poor antiproliferative response to an aromatase inhibitor(AI) who may derive greatest benefit from additional adjuvant endocrine therapy with abemaciclib.
Key Eligibility Criteria for registration:• ER+, HER2-• Postmenopausal• Palpable tumour of any size or ≥1.5cm by imaging
• Baseline Ki67 ≥ 20% measured at the local siteOR
• presence of clinico-pathologic factors that predict (>50% chance) patients with Ki67 ≥ 8% after 2weeks’ AI, i.e. grade 3; clinical/radiological tumour size > 5cm; PgR negative or PgR unknown ANDevidence of vascular invasion.
Eligibility for randomisation: 1. Centrally confirmed Ki67 >8% following 2 weeks of AI.
2. Completed surgery, chemotherapy and radiotherapy (if prescribed) with any previous toxicities resolved to grade 1 or 0.
POETIC-A Pre-Operative Endocrine Therapy for Individualised Care with Abemaciclib
Randomisation: Patients who remain eligible will be formally entered into the randomised trial
and allocated to ± abemaciclib (1:1 allocation ratio) with stratification by the AIR-CIS signature
(dichotomised). There will be no placebo control, consistent with Monarch-E. Treatment with
endocrine therapy (AI) will be given until evidence of disease recurrence or for planned duration of
therapy.
Treatment period: patients in the abemaciclib arm will receive abemaciclib 150mg for 2 years. All
patients will receive standard adjuvant endocrine therapy for a minimum of 5 years. Patients will
have on-treatment visits for 2 years and follow-up visits at 3, 4, and 5 years post-randomisation.
Sample size and recruitment period:
6000 early breast cancer patients registered from approx. 80 UK centres, 2500 randomised over 3
years.
POETIC-A Team
Chief Investigator: Professor Stephen Johnston Coordinating Investigator: Dr Alistair RingTranslational Study Lead: Prof Mitch DowsettScientific/Methodology Lead: Prof Judith BlissBioinformatics and Genomic Analysis Lead: Dr Maggie Cheang
Coordinating Clinical Trials Unit: ICR-CTSU• Clinical Trials Programme Manager: Hilda Tsang• Trial Manager: Peter Chatfield
Sponsor: The Institute of Cancer Research
POETIC-A-icrctsu@icr.ac.uk
Tel: +44 (0)208 722 4264
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