Making Precision Decisions in High-Risk HR+, HER2- Metastatic Breast Cancer: Practical Training on Individualizing CDK4/6 Inhibitor Treatment to Enhance Adherence, Quality of Life, and Outcomes
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Sep 18, 2024
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About This Presentation
Chair Stephanie L. Graff, MD, FACP, FASCO, discusses breast cancer in this CME/MOC/NCPD/CPE/AAPA/IPCE activity titled “Making Precision Decisions in High-Risk HR+, HER2- Metastatic Breast Cancer: Practical Training on Individualizing CDK4/6 Inhibitor Treatment to Enhance Adherence, Quality of Life...
Slide Content
Making Precision Decisions in High-Risk
HR+, HER2- Metastatic Breast Cancer
Practical Training on Individualizing CDK4/6 Inhibitor Treatment
to Enhance Adherence, Quality of Life, and Outcomes
Stephanie L. Graff, MD, FACP, FASCO
Associate Professor of Medicine
Brown University
Director of the Breast Oncology Program
Lifespan Cancer Institute
Co-leader of the Breast Cancer Translational Research Disease Group
Providence, Rhode Island
0-2024, PeerView
HR+, HER2- Metastatic Breast Cancer
Practical Training on Individualizing CDK4/6 Inhibitor Treatment
to Enhance Adherence, Quality of Life, and Outcomes
Stephanie L. Graff, MD, FACP, FASCO
Associate Professor of Medicine
Brown University
Director of the Breast Oncology Program
Lifespan Cancer Institute
Co-leader of the Breast Cancer Translational Research Disease Group
Providence, Rhode Island
0-2024, PeerView
Addressing Gaps and Challenges in HR+, HER2- Metastatic
Breast Cancer Care: Reasons for This Educational Session
A combination of a CDK4/6 inhibitor and endocrine agent is the 1L SOC
in HR+, HER2- MBC, but it has been unclear if the three available CDK4/6
inhibitors can be used interchangeably
How can we explain the variable OS findings in different 1L trials? >
What are the real-world implications for treatment selection? >
How can we ensure patients can stay on therapy and derive maximum benefit?
Benefits of continuing CDK4/6 inhibitor beyond progression have
been unclear, but new evidence has recently emerged
What are the clinical implications for treatment selection and sequencing?
idualized approach to treatment selectio:
sequencing, and delivery in HR+, HER2- MBC
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PeerView.com/AGR827
Breast Cancer Care: Reasons for This Educational Session
A combination of a CDK4/6 inhibitor and endocrine agent is the 1L SOC
in HR+, HER2- MBC, but it has been unclear if the three available CDK4/6
inhibitors can be used interchangeably
How can we explain the variable OS findings in different 1L trials? >
What are the real-world implications for treatment selection? >
How can we ensure patients can stay on therapy and derive maximum benefit?
Benefits of continuing CDK4/6 inhibitor beyond progression have
been unclear, but new evidence has recently emerged
What are the clinical implications for treatment selection and sequencing?
idualized approach to treatment selectio:
sequencing, and delivery in HR+, HER2- MBC
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PeerView.com/AGR827
Our Goals for Today
Augment your knowledge of the characteristics and efficacy/safety
profiles of the CDK4/6 inhibitors in HR+, HER2- MBC
Equip you with skills to formulate individualized treatment plans for
patients with HR+, HER2- MBC based on the latest evidence and
relevant key factors
Enhance best practices for implementing team-based strategies to
anticipate, detect, and manage AEs and improve adherence/persistence
in HR+, HER2- MBC
Augment your knowledge of the characteristics and efficacy/safety
profiles of the CDK4/6 inhibitors in HR+, HER2- MBC
Equip you with skills to formulate individualized treatment plans for
patients with HR+, HER2- MBC based on the latest evidence and
relevant key factors
Enhance best practices for implementing team-based strategies to
anticipate, detect, and manage AEs and improve adherence/persistence
in HR+, HER2- MBC
MAKING PRECISION DECISIONS IN HIGH-RISK HR+, HER2- METASTATIC BREAST CANCER | OUTLINE
| PART1
PART 2
Making Multifactorial Clinical Decisions
About the Selection and Use of Fi line
CDK4/6 Inhibitors in High-Risk
HR+, HER2- MBC
PeerView.co
Managing Adverse Events, Improving
Adherence/Persistence, and Maximizing
Treatment Benefits of CDK4/6 Inhibitors
Copyright © 2000
| PART1
PART 2
Making Multifactorial Clinical Decisions
About the Selection and Use of Fi line
CDK4/6 Inhibitors in High-Risk
HR+, HER2- MBC
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Managing Adverse Events, Improving
Adherence/Persistence, and Maximizing
Treatment Benefits of CDK4/6 Inhibitors
Copyright © 2000
Introduction to Case 1: 1L Therapy for a Patient
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive carcinoma of
the breast (ductal), pT2N1, grade 3, ER+, PgR-, HER2-
History: Mammogram/US showed a 2.9-cm mass + enlarged, suspicious axillary LN
- Underwent lumpectomy > adjuvant chemotherapy (TC) > breast RT > adjuvant Al
- Patient has a long-standing history of bipolar disorder, well controlled on quetiapine
‘Two years after starting Al develops right hip pain > bone scan reveals lytic bone lesions
CT C/A/P also shows numerous liver and bone metastases involving spine, hip, and ribs
Biopsy of the liver shows ER+, PgR-, HER2- carcinoma c/w breast
Blood work shows normal liver function studies
BRCA1/2-
Baseline EKG: QTc 575 ms
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With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive carcinoma of
the breast (ductal), pT2N1, grade 3, ER+, PgR-, HER2-
History: Mammogram/US showed a 2.9-cm mass + enlarged, suspicious axillary LN
- Underwent lumpectomy > adjuvant chemotherapy (TC) > breast RT > adjuvant Al
- Patient has a long-standing history of bipolar disorder, well controlled on quetiapine
‘Two years after starting Al develops right hip pain > bone scan reveals lytic bone lesions
CT C/A/P also shows numerous liver and bone metastases involving spine, hip, and ribs
Biopsy of the liver shows ER+, PgR-, HER2- carcinoma c/w breast
Blood work shows normal liver function studies
BRCA1/2-
Baseline EKG: QTc 575 ms
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Differences Among the CDK4/6 Inhibitors:
Are They Significant and Relevant?!
+ All CDK4/6 inhibitors (CDK4/6is) inhibit CDK4/6 complexes; palbociclib and ribociclib have a high selectivity for CDK4 and CDK6, but
ribociclib has a higher CDK4:CDK6 inhibition ratio (-4) given its weaker potency for inhibition of CDK6
ith a CDK4:CDK6 inhibition ratio of 5,
a strong and sustained apoptotic effect— it has cyclin B-
+ Abemacidlib has a different chemical structure and exhibits the highest inhibitory effect on CDK4/6
and additional activity on multiple kinases—making it more potent and indu
CDK1, cyclin AE-CDK2, and cyclin T-CDK9 inhibition
Target Spectra of Approved CDK4/6 Inhil
E COKAteyesn os. CET E
cyclin e Gly cyclin ER Aooracicib
ofa | “inhib
Dr-coR« 5 = 8-coki T-CDko Cokziyein at Mec
cDk4 Ratio
coca Lise
Ea " te mé MR cotes
>s0 40 1 03 091 000ı]
20 ta 113000 76000 NR coKeiyein D1 ICM)
oki Ti
5 Te = er Er 5 COKeychn ARANA TA
COKBIeyoin k
( Different acquired resistance mechanisms demonstrated in a high-resolution analysis of preclinical models
‘Col Chem Bio 2019:26:1067-1080 28.2. Sammons SL et al. Cur Cancer Drug Target. 2017:17:537-649.
1. ASCO 2022 4, Guarducci C et al, Cancer Ros. 202323:059-G807.
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Are They Significant and Relevant?!
+ All CDK4/6 inhibitors (CDK4/6is) inhibit CDK4/6 complexes; palbociclib and ribociclib have a high selectivity for CDK4 and CDK6, but
ribociclib has a higher CDK4:CDK6 inhibition ratio (-4) given its weaker potency for inhibition of CDK6
ith a CDK4:CDK6 inhibition ratio of 5,
a strong and sustained apoptotic effect— it has cyclin B-
+ Abemacidlib has a different chemical structure and exhibits the highest inhibitory effect on CDK4/6
and additional activity on multiple kinases—making it more potent and indu
CDK1, cyclin AE-CDK2, and cyclin T-CDK9 inhibition
Target Spectra of Approved CDK4/6 Inhil
E COKAteyesn os. CET E
cyclin e Gly cyclin ER Aooracicib
ofa | “inhib
Dr-coR« 5 = 8-coki T-CDko Cokziyein at Mec
cDk4 Ratio
coca Lise
Ea " te mé MR cotes
>s0 40 1 03 091 000ı]
20 ta 113000 76000 NR coKeiyein D1 ICM)
oki Ti
5 Te = er Er 5 COKeychn ARANA TA
COKBIeyoin k
( Different acquired resistance mechanisms demonstrated in a high-resolution analysis of preclinical models
‘Col Chem Bio 2019:26:1067-1080 28.2. Sammons SL et al. Cur Cancer Drug Target. 2017:17:537-649.
1. ASCO 2022 4, Guarducci C et al, Cancer Ros. 202323:059-G807.
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Clinical Differences Among the CDK4/6 Inhibitors
‘Abemaciclib is dosed continuously, while ribociclib and palbociclib are administered intermittently
Ribociclib is the only CDK4/6i tested in pre- and perimenopausal patients
Abemaciclib penetrates the blood-brain barrier and is the only CDK4/6i tested in patients with HR+ brain
metastases
Abemaciclib is the only CDK4/6i with proven single-agent activity
+ There are differences in toxicity profiles and monitoring needs
— Abemaciclib causes predominantly GI toxicities, whereas palbociclib and ribociclib are characterized
by hematologic toxicities
— Both abemaciclib and ribociclib require liver function monitoring
- Ribociclib may prolong the QTe interval > ECG monitoring needed during first 2 cycles
+ In MBC, clinical trials showed similar PFS for all three agents but differences in OS outcomes in phase 3
RCTs
Let’s explore the data in more detail PeerView.com
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‘Abemaciclib is dosed continuously, while ribociclib and palbociclib are administered intermittently
Ribociclib is the only CDK4/6i tested in pre- and perimenopausal patients
Abemaciclib penetrates the blood-brain barrier and is the only CDK4/6i tested in patients with HR+ brain
metastases
Abemaciclib is the only CDK4/6i with proven single-agent activity
+ There are differences in toxicity profiles and monitoring needs
— Abemaciclib causes predominantly GI toxicities, whereas palbociclib and ribociclib are characterized
by hematologic toxicities
— Both abemaciclib and ribociclib require liver function monitoring
- Ribociclib may prolong the QTe interval > ECG monitoring needed during first 2 cycles
+ In MBC, clinical trials showed similar PFS for all three agents but differences in OS outcomes in phase 3
RCTs
Let’s explore the data in more detail PeerView.com
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Big Picture Overview: Phase 3 CDK4/6i Trials Show
Consistent PFS Benefit in the 1L Setting of MBC'>
| PALOMA-1 | PALOMA-2 | MONALEESA-2 | MONARCH 3 | MONALEESA-3
: Phase 2 Phase 3 Phase 3 Phase 3 Phase 3
Design AL AL AL AL AL and 2L
endosring Letrozole Letrozole Letrozole Leon Fulvestrant
Partner anastrozole
Palbociclib Palbociclib Ribociclib Abemaciclib Ribociclib
Patients on
Study, n
HR
25.3 vs 16
33.6 vs 19.2
20.2 vs 10.2 24.8 vs 14.5 28.18 vs 14.76
1. Finn RS etal. Lancet Oncol. 2015:1625-35.2. Finn RS at al. MEnglJ Med 2016:378:1925-1998, 3. Hortbagy GN et al. Ann Oncol. 2018:20:1541-1547. E
4. Johnston Se al. NP Breast Concer. 2019:55, 5. Slamon Du et al. N Engl J Mod. 2020;382:514-524, PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Consistent PFS Benefit in the 1L Setting of MBC'>
| PALOMA-1 | PALOMA-2 | MONALEESA-2 | MONARCH 3 | MONALEESA-3
: Phase 2 Phase 3 Phase 3 Phase 3 Phase 3
Design AL AL AL AL AL and 2L
endosring Letrozole Letrozole Letrozole Leon Fulvestrant
Partner anastrozole
Palbociclib Palbociclib Ribociclib Abemaciclib Ribociclib
Patients on
Study, n
HR
25.3 vs 16
33.6 vs 19.2
20.2 vs 10.2 24.8 vs 14.5 28.18 vs 14.76
1. Finn RS etal. Lancet Oncol. 2015:1625-35.2. Finn RS at al. MEnglJ Med 2016:378:1925-1998, 3. Hortbagy GN et al. Ann Oncol. 2018:20:1541-1547. E
4. Johnston Se al. NP Breast Concer. 2019:55, 5. Slamon Du et al. N Engl J Mod. 2020;382:514-524, PeerView.com
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Big Picture Overview: Differences in OS Results
in Phase 3 CDK4/6i Trials in 1L Setting of MBC*-3
PALOMA! 0.956
= HB
Z Palbociib + ltrozole 29 se Gt |
PALOMA-3 o yl 0.81
Palbociclib + fulvestrant Ene) ea (064-103 8 ES
MONARCH 2° = 076
© Abemaciclib +fulvestrant el gy ws % 4
MONARCH 3¢ —s—h 0.804
Abemacicib + NSAI ee nr ws (4 XK
MONALEESA 2° 076
Ribociclib + letrazole ES pus a (ossoss, MY
o
MONALEESA-77
a ; om
2 ib + goserelin + as
D des Rs cn A
072
NR 40.0 a DA
| AP ee Se
04 06 08 10 12
RE en”
he 16 dns wo at ro po ia mean OS conse ps
TR EP A ape et TROP Tone Ne oe hE Mad 201-103 Sign O al JAUA net 20206 11-1244 Got Pt
‘havoc 2st) aL ag che Eng hg 202009420 À Yang GN ta ESMO 201 Da LAT PR mba NEM ae en
2910:381.307:316. 8. Somon D tl. N Engl Mod. 2020:362313-524. PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
in Phase 3 CDK4/6i Trials in 1L Setting of MBC*-3
PALOMA! 0.956
= HB
Z Palbociib + ltrozole 29 se Gt |
PALOMA-3 o yl 0.81
Palbociclib + fulvestrant Ene) ea (064-103 8 ES
MONARCH 2° = 076
© Abemaciclib +fulvestrant el gy ws % 4
MONARCH 3¢ —s—h 0.804
Abemacicib + NSAI ee nr ws (4 XK
MONALEESA 2° 076
Ribociclib + letrazole ES pus a (ossoss, MY
o
MONALEESA-77
a ; om
2 ib + goserelin + as
D des Rs cn A
072
NR 40.0 a DA
| AP ee Se
04 06 08 10 12
RE en”
he 16 dns wo at ro po ia mean OS conse ps
TR EP A ape et TROP Tone Ne oe hE Mad 201-103 Sign O al JAUA net 20206 11-1244 Got Pt
‘havoc 2st) aL ag che Eng hg 202009420 À Yang GN ta ESMO 201 Da LAT PR mba NEM ae en
2910:381.307:316. 8. Somon D tl. N Engl Mod. 2020:362313-524. PeerView.com
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Phase 3 MONALEESA-2: First-Line Al + Ribociclib
HR+/HER2- MBC"
Median OS, mo (95% Cl)
Ribociclib (n = 334): 63.9
Placebo (n = 334): 51.4
HR = 0.76 (95% Cl, 0.63-0.93)
P= 008
Ribociclib
OS, %
8
Placebo
ot — r
0 4 & de te 20 de de de 36 do da de s2 co do G4 68 72 76 80 84 88
Time, mo
Ribociclib + letrozole showed a significant OS benefit, with a 1-year improvement over placebo in
HR+/HER2- advanced breast cancer > new benchmark for OS in the first-line setting of over 5 years
(A EEE BT
1 Horobogyi GN etal.N Engl Med. 2022.366:942:960. PeerView.com
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HR+/HER2- MBC"
Median OS, mo (95% Cl)
Ribociclib (n = 334): 63.9
Placebo (n = 334): 51.4
HR = 0.76 (95% Cl, 0.63-0.93)
P= 008
Ribociclib
OS, %
8
Placebo
ot — r
0 4 & de te 20 de de de 36 do da de s2 co do G4 68 72 76 80 84 88
Time, mo
Ribociclib + letrozole showed a significant OS benefit, with a 1-year improvement over placebo in
HR+/HER2- advanced breast cancer > new benchmark for OS in the first-line setting of over 5 years
(A EEE BT
1 Horobogyi GN etal.N Engl Med. 2022.366:942:960. PeerView.com
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PALOMA-2 First-Line Letrozole + Palbociclib:
Overall Survival Analysis?
os: ITT Post-Hoc Sensitivity Analysis: Excluding
Patients With Survival Data Not Available
Median Follow PAL+LET PBO+LET
non) 30 months. 5) “tne 175)
Modan 08, me 3 2 100 Megan 05,70 5 Er
e ch 498600) (37569) (85% CI) ws 670822)
x Seated HR 0956 5 Unstatfied HR 0260
5 165% ch) Curl à (95% ch (0706-1069)
zo 1-sided P 3378 2
3 qa
2» PAS LED 2 PAL+LET
8% Bg
o o
0 CS IEEE TE (WO
hos Der Time, mo
+ Median follow-up: 7.5 years
+ Missing survival data: 13% palbociciib + letrozole and 21% control
+ More crossover to CDK4/ in the control arm, 27% vs 12%
+ 10% of patients continued on palbociclib and letrozole at 7.5-year follow-up
1. Finn RS al. J Gin Oncol 2022: 40(17}:LBA1005-LBA1008. PeerView.com
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Overall Survival Analysis?
os: ITT Post-Hoc Sensitivity Analysis: Excluding
Patients With Survival Data Not Available
Median Follow PAL+LET PBO+LET
non) 30 months. 5) “tne 175)
Modan 08, me 3 2 100 Megan 05,70 5 Er
e ch 498600) (37569) (85% CI) ws 670822)
x Seated HR 0956 5 Unstatfied HR 0260
5 165% ch) Curl à (95% ch (0706-1069)
zo 1-sided P 3378 2
3 qa
2» PAS LED 2 PAL+LET
8% Bg
o o
0 CS IEEE TE (WO
hos Der Time, mo
+ Median follow-up: 7.5 years
+ Missing survival data: 13% palbociciib + letrozole and 21% control
+ More crossover to CDK4/ in the control arm, 27% vs 12%
+ 10% of patients continued on palbociclib and letrozole at 7.5-year follow-up
1. Finn RS al. J Gin Oncol 2022: 40(17}:LBA1005-LBA1008. PeerView.com
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Real-World Overall Survival Data for Palbociclib
Before and After sIPTW and PSM: P-REALITY X!
soy Unadjusted Analysis = sIPTW = PsM
=. Re para a PAL+ as
8 = y
8
ET ma 2 Mode os me 41 432 zlmamosme a ss
ose) e cards) CRC) un (78480) GRO) (ANT 7649)
| rita 0% 6.060070) < om of HR=076 05% C1 065.087: P= 0001 ol ARTE 66% 1 amas) P < 0001
Time, mo Time, mo. Time, mo
Median Temp. Saone Dr
Mn lensP aso (130003) 223118429) een tower 9128300) 245 (12042) EEE ET]
Median OS: was significantly longer among patients who received PAL + Al vs Al alone before and after sIPTW and PSM
Note: Observational retrospective analyses are designed to evaluate associations among variables and cannot establish causality;
they are not intended for direct comparison with clinical trials.
+05 was defines as the time in months fom the index date o death rom any causo. ee
1. Rugo H ot al ESMO BC 2022, Poser 189°. PeerView.com
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Before and After sIPTW and PSM: P-REALITY X!
soy Unadjusted Analysis = sIPTW = PsM
=. Re para a PAL+ as
8 = y
8
ET ma 2 Mode os me 41 432 zlmamosme a ss
ose) e cards) CRC) un (78480) GRO) (ANT 7649)
| rita 0% 6.060070) < om of HR=076 05% C1 065.087: P= 0001 ol ARTE 66% 1 amas) P < 0001
Time, mo Time, mo. Time, mo
Median Temp. Saone Dr
Mn lensP aso (130003) 223118429) een tower 9128300) 245 (12042) EEE ET]
Median OS: was significantly longer among patients who received PAL + Al vs Al alone before and after sIPTW and PSM
Note: Observational retrospective analyses are designed to evaluate associations among variables and cannot establish causality;
they are not intended for direct comparison with clinical trials.
+05 was defines as the time in months fom the index date o death rom any causo. ee
1. Rugo H ot al ESMO BC 2022, Poser 189°. PeerView.com
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MONARCH-3: First-Line Al + Abemaciclib
HR+/HER2- advanced BC
+ Postmenopausal
Abemaciclib 150 mg PO BID +
anastrozole 1 mg or letrozole 2.5 mg
+ Metastatic or locoregionally recurrent disease PO QD until PD
with no prior systemic therapy in this setting
+ If (neo)adjuvant ET administered, a disease-
free interval of >12 months since completion
of ET
+ ECOG PS 0-1
Stratified by
+ Metastatic site (visceral, bone only, or other)
+ Prior ET (Al, no ET, or other)
(N = 493)
Placebo PO BID + anastrozole 1 mg
or letrozole 2.5 mg PO QD until PD
+ Primary endpoint: investigator-assessed PFS
+ Key secondary endpoints: OS, response
rates, and safety
1. Goetz MP eta. Ann Oncol 2022:38:8808-S869, 2. Goetz MP eta. Ann Oncol 2024;35(8):718-727. PeerView.com
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HR+/HER2- advanced BC
+ Postmenopausal
Abemaciclib 150 mg PO BID +
anastrozole 1 mg or letrozole 2.5 mg
+ Metastatic or locoregionally recurrent disease PO QD until PD
with no prior systemic therapy in this setting
+ If (neo)adjuvant ET administered, a disease-
free interval of >12 months since completion
of ET
+ ECOG PS 0-1
Stratified by
+ Metastatic site (visceral, bone only, or other)
+ Prior ET (Al, no ET, or other)
(N = 493)
Placebo PO BID + anastrozole 1 mg
or letrozole 2.5 mg PO QD until PD
+ Primary endpoint: investigator-assessed PFS
+ Key secondary endpoints: OS, response
rates, and safety
1. Goetz MP eta. Ann Oncol 2022:38:8808-S869, 2. Goetz MP eta. Ann Oncol 2024;35(8):718-727. PeerView.com
PeerView.com/AGR827 Copyright O 2000-2024, PeerView
MONARCH-3: Final OS in the ITT Population’?
Abemaciclib+ Placebo +
El NSAI NSAI
= Median OS, mo 66.8 537
n ‘Abemaciclib + NSAI
m HR (95%) 0.804 (0.637-1.015)
# 2:sided P 0664
go
« Preplanned OS analysis
5 Data cut: Sept 29, 2023
»
‘Abemacicb + NSAI 328 198(60%)
Placobo + NSAI CET)
0 6 RDM D % & & 4 © S À mn MM“ 1%
Nat Risk Time, mo
Rand eNSN 320 M ZU 200 AT 229 21 We 7 NA 166 We ATHY 1 ww
Abemaciclib + NSAI resulted in a numerically longer OS vs NSAI alone; clinically significant
but statistical significance was not reached; the observed improvement in median OS was 13.1 months
© —
"Di not reach threshold (0.034) or statistical sigaiicance at ns A
1. Goetz MP eta. SABCS 2023, Abstract GS01-12. 2 Goetz MP at
“an col 2024950971827. PeerView.com
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Abemaciclib+ Placebo +
El NSAI NSAI
= Median OS, mo 66.8 537
n ‘Abemaciclib + NSAI
m HR (95%) 0.804 (0.637-1.015)
# 2:sided P 0664
go
« Preplanned OS analysis
5 Data cut: Sept 29, 2023
»
‘Abemacicb + NSAI 328 198(60%)
Placobo + NSAI CET)
0 6 RDM D % & & 4 © S À mn MM“ 1%
Nat Risk Time, mo
Rand eNSN 320 M ZU 200 AT 229 21 We 7 NA 166 We ATHY 1 ww
Abemaciclib + NSAI resulted in a numerically longer OS vs NSAI alone; clinically significant
but statistical significance was not reached; the observed improvement in median OS was 13.1 months
© —
"Di not reach threshold (0.034) or statistical sigaiicance at ns A
1. Goetz MP eta. SABCS 2023, Abstract GS01-12. 2 Goetz MP at
“an col 2024950971827. PeerView.com
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MONARCH-3: OS in the Subgroup With
Visceral Disease‘?
100 Abemaciclib +NSAI Placebo + NSAI
s Median OS, mo 637 488
30 HR (95%) 0.758 (0.558-1.030)
” 2-sided P 0757
63.7 mo (A= 14.9)
OS, %
Abemaciclib + NSAI
Placebo + NSAI
Patients, n Events, n(%)
‘Abomacicb + NSAI m 365)
Placebo + NSAI 9 65 (72)
0 6 12 18 24 30 36 42 48 54 Go 65 72 78 8% 90 96
Be Time, mo
Abomaciclb + NSAI 173 161 147 138 126 118 107 100 95 86 78 72 63 53 46 45 27 3
Abemaciclib + NSAI resulted in a numerically longer OS compared with NSAI alone in the sVD; clinically significant
but statistical significance was not reached; the observed improvement in median OS was 14.9 months
Did not reach Ireshol (0.008) or stastealsigniicance ats fal ana. =.
1. Goetz MP a al SABCS 2023, Abstract 6801-12.2. Gootz MP et al. Ann Oncol, 2024:350)718:727. PeerView.com
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Visceral Disease‘?
100 Abemaciclib +NSAI Placebo + NSAI
s Median OS, mo 637 488
30 HR (95%) 0.758 (0.558-1.030)
” 2-sided P 0757
63.7 mo (A= 14.9)
OS, %
Abemaciclib + NSAI
Placebo + NSAI
Patients, n Events, n(%)
‘Abomacicb + NSAI m 365)
Placebo + NSAI 9 65 (72)
0 6 12 18 24 30 36 42 48 54 Go 65 72 78 8% 90 96
Be Time, mo
Abomaciclb + NSAI 173 161 147 138 126 118 107 100 95 86 78 72 63 53 46 45 27 3
Abemaciclib + NSAI resulted in a numerically longer OS compared with NSAI alone in the sVD; clinically significant
but statistical significance was not reached; the observed improvement in median OS was 14.9 months
Did not reach Ireshol (0.008) or stastealsigniicance ats fal ana. =.
1. Goetz MP a al SABCS 2023, Abstract 6801-12.2. Gootz MP et al. Ann Oncol, 2024:350)718:727. PeerView.com
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MONARCH-3: OS in Subgroups’
41. Goetz MP
PeerView.com/AGR827
Exento N neos e
da one
Voce ms vs 0755 0556-1028)
Bone oy ie 0396 0.300097),
Ou mn voran
Endocrine therapy 0205
Por semé or Persos CR 0825 03700859),
(tres po encore merapy > à 09420 58-119)
No se nenne herr mom Bars (OS 1202)
Diana eating aan
De new met se CE 0747 (517-1079
Mae rent Sas CR (3794 (8061 000)
Number organs at bol 048
ES mm 1 0887 (0520-1188)
2 mn 386 080.130)
4 wm (608 (038-0952)
Aga year oz
= am er ors (0502-1118)
2 z= ww 0751 (0500-1089)
ace ou
‘cavoan ms 19s og 6201122
Sa won 0878 (0426-1050)
Progesterone receptor status oo
Negative won 0490 03140700)
Poste ss 26 ans (0678-10)
Basing 200 PS 06%
ñ oo 0721 (0507-1028)
o 2 (201 0501-1980)
0% os om
Furs PSE
1
Fever acute
HRs for abemaciclib versus placebo arm were consistent across subgroups with respect to prognosis and
endocrine sensitivity, with a numerically greater effect observed in patients with bone-only disease, progesterone
receptor negative tumors,
1 SABCS 2023. Asta 0801.12 2. Goetz MP at al Ann Once! 202435(9/718727.
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41. Goetz MP
PeerView.com/AGR827
Exento N neos e
da one
Voce ms vs 0755 0556-1028)
Bone oy ie 0396 0.300097),
Ou mn voran
Endocrine therapy 0205
Por semé or Persos CR 0825 03700859),
(tres po encore merapy > à 09420 58-119)
No se nenne herr mom Bars (OS 1202)
Diana eating aan
De new met se CE 0747 (517-1079
Mae rent Sas CR (3794 (8061 000)
Number organs at bol 048
ES mm 1 0887 (0520-1188)
2 mn 386 080.130)
4 wm (608 (038-0952)
Aga year oz
= am er ors (0502-1118)
2 z= ww 0751 (0500-1089)
ace ou
‘cavoan ms 19s og 6201122
Sa won 0878 (0426-1050)
Progesterone receptor status oo
Negative won 0490 03140700)
Poste ss 26 ans (0678-10)
Basing 200 PS 06%
ñ oo 0721 (0507-1028)
o 2 (201 0501-1980)
0% os om
Furs PSE
1
Fever acute
HRs for abemaciclib versus placebo arm were consistent across subgroups with respect to prognosis and
endocrine sensitivity, with a numerically greater effect observed in patients with bone-only disease, progesterone
receptor negative tumors,
1 SABCS 2023. Asta 0801.12 2. Goetz MP at al Ann Once! 202435(9/718727.
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MONARCH-3: Updated PFS in the ITT Population’?
100
90
80
Abemaciclib + NSAI Placebo + NSAI
Median PFS, mo 29.0 148
E z HR (95%) 0.535 (0.535 (0.429-0.668)
50 29.0 mo (A = 14.3) Nominal P 0001®
PFS, %
40
30
20
10
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96
No. at Risk melo]
Abemacidlb + NSAI 328 251 209 173 143 121 99 86 76 61 54 45 41 39 31 25 10
Plæsbo+ NSAI 165114 88 61 51 31 21 19 15 13 11 7 5 5 5 3 0
The addition of abemaciclib to NSAI resulted in a 14.3-month improvement in median PFS
with continued separation of the curves at longer follow-up
+ Staistea significance was reached atte iter PFS =
1. Goetz MP at a. SABCS 2023, Abstract 6801-12.2. Gootz MP ta. Ann Oncol 2024:350)718:727. PeerView.com
Copyright © 2000-2024, Peerview
MONARCH-3: Updated PFS in the ITT Population’?
100
90
80
Abemaciclib + NSAI Placebo + NSAI
Median PFS, mo 29.0 148
E z HR (95%) 0.535 (0.535 (0.429-0.668)
50 29.0 mo (A = 14.3) Nominal P 0001®
PFS, %
40
30
20
10
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96
No. at Risk melo]
Abemacidlb + NSAI 328 251 209 173 143 121 99 86 76 61 54 45 41 39 31 25 10
Plæsbo+ NSAI 165114 88 61 51 31 21 19 15 13 11 7 5 5 5 3 0
The addition of abemaciclib to NSAI resulted in a 14.3-month improvement in median PFS
with continued separation of the curves at longer follow-up
+ Staistea significance was reached atte iter PFS =
1. Goetz MP at a. SABCS 2023, Abstract 6801-12.2. Gootz MP ta. Ann Oncol 2024:350)718:727. PeerView.com
Copyright © 2000-2024, Peerview
MONARCH-3: Updated PFS in Subgroups'?
EventsIN HR (95% CI) P Median, mo
Abema+ AI Placebo + Al
mr 2931493 0.525 (0415-0665) 282 148
Baseline ECOG PS.
o 178296 0512030680) 795 282 157
1 115/197 0,546 (0373-0798) 290 142
Bone-only metastasis
Yes STD 0471(0.280-0799) zp 389 266
No 236384 0511 (0.393-0.665) 27.0 128
Liver metastasis
No 2411815 0.596 (0414-0693) gs 31 165
Yes 5278 0.449 (0.259-0.777) 150 72
Progesterone receptor status
Positive 2211983 0.555 (0424-0726) 345 EN] 156
Negative 70/06 0.427 (0.265-0.687) 270 94
Tumor grade
Lowintermediate 170275 054304000737) agg 270 149
High 5697 0.322 (0.190-0.546) 353 90
Treatment-froe survival
236 months 82/136 0.689(0.438-1.084) 500 270 209
36 months 5076 0.418 (0 240-0 729) 2 90
92 0408 08 À
Favors abemaciclib +Al Favors placebo + Al
Treatment benefit observed across all subgroups, with the largest effects observed in patients with liver metastases,
progesterone receptor-negative tumors, high-grade tumors, or TFI <36 months
1. Goetz MP etal. SABCS 2023. Abstract GSO1-12, 2. Goetz MP etal. Ann Oncol. 2024:26(8)718-727. PeerView.com
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EventsIN HR (95% CI) P Median, mo
Abema+ AI Placebo + Al
mr 2931493 0.525 (0415-0665) 282 148
Baseline ECOG PS.
o 178296 0512030680) 795 282 157
1 115/197 0,546 (0373-0798) 290 142
Bone-only metastasis
Yes STD 0471(0.280-0799) zp 389 266
No 236384 0511 (0.393-0.665) 27.0 128
Liver metastasis
No 2411815 0.596 (0414-0693) gs 31 165
Yes 5278 0.449 (0.259-0.777) 150 72
Progesterone receptor status
Positive 2211983 0.555 (0424-0726) 345 EN] 156
Negative 70/06 0.427 (0.265-0.687) 270 94
Tumor grade
Lowintermediate 170275 054304000737) agg 270 149
High 5697 0.322 (0.190-0.546) 353 90
Treatment-froe survival
236 months 82/136 0.689(0.438-1.084) 500 270 209
36 months 5076 0.418 (0 240-0 729) 2 90
92 0408 08 À
Favors abemaciclib +Al Favors placebo + Al
Treatment benefit observed across all subgroups, with the largest effects observed in patients with liver metastases,
progesterone receptor-negative tumors, high-grade tumors, or TFI <36 months
1. Goetz MP etal. SABCS 2023. Abstract GSO1-12, 2. Goetz MP etal. Ann Oncol. 2024:26(8)718-727. PeerView.com
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Summary and Context: Comparing OS Analyses in
MONARCH-3 and MONALEESA-2*
MONARCH-3 MONALEESA-2
Median follow-up, y 8 (96 mo, final OS) 5.8 (70 mo, IA2OS) 6.6 (80 mo)
Abema + Al PBO +Al Abema + Al PBO +AI RIB + Al PBO +AI
328 165 328 165 334 334
Deaths, n (%) 198/328 (60) 116/165 (70) | 158/328 (48) 97/165 (59) | 181/334 (54) 2191334 (66)
Poststudy CDK4/6i, % 12 32 - - 22 34
67 54 67 54 64 (52-71) 51 (47-60)
0.754 (0.58-0.974);
P=.0301
4. Tolaney S. SABCS 2023. Viow From the Tronchos"Presontaton,
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MONARCH-3 and MONALEESA-2*
MONARCH-3 MONALEESA-2
Median follow-up, y 8 (96 mo, final OS) 5.8 (70 mo, IA2OS) 6.6 (80 mo)
Abema + Al PBO +Al Abema + Al PBO +AI RIB + Al PBO +AI
328 165 328 165 334 334
Deaths, n (%) 198/328 (60) 116/165 (70) | 158/328 (48) 97/165 (59) | 181/334 (54) 2191334 (66)
Poststudy CDK4/6i, % 12 32 - - 22 34
67 54 67 54 64 (52-71) 51 (47-60)
0.754 (0.58-0.974);
P=.0301
4. Tolaney S. SABCS 2023. Viow From the Tronchos"Presontaton,
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MONARCH-3: Summary and Context
Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT populatio
Consistent OS effect size was seen across all subgroups, notably in patients with:
~ Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
Effect size was consistent in de novo and recurrent metastatic disease
Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT populatio
Consistent OS effect size was seen across all subgroups, notably in patients with:
~ Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
Effect size was consistent in de novo and recurrent metastatic disease
Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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MONARCH-3: Summary and Context
Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
+ Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with
liver metastases the addition of ribociclib to letroz: MONALEESA-2) i
+ Effect size was consistent in de novo and recurrent metastatic disease
+ Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
+ MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
+ Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with
liver metastases the addition of ribociclib to letroz: MONALEESA-2) i
+ Effect size was consistent in de novo and recurrent metastatic disease
+ Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
+ MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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MONARCH-3: Summary and Context
Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
u 2 E = = =
+ Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
+ MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
u 2 E = = =
+ Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
+ MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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MONARCH-3: Summary and Context
Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
+ Effect size was consistent in de novo and recurrent metastatic disease
+ MONARCH:3 OS data are consistent with the findings i in MONARCH-2, where the ‘addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
+ Effect size was consistent in de novo and recurrent metastatic disease
+ MONARCH:3 OS data are consistent with the findings i in MONARCH-2, where the ‘addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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MONARCH-3: Summary and Context
Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
+ Effect size was consistent in de novo and recurrent metastatic disease
+_ Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
+ MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of 1
abemaciclib to fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance |
+ Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
+ Effect size was consistent in de novo and recurrent metastatic disease
+_ Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
+ MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of 1
abemaciclib to fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance |
+ Lack of statistical significance in this final OS analysis may be viewed as a limitation, but itis important to
consider the clinical relevance of the absolute effect size in the context of the limitations of the study design
(smaller sample size than that in PALOMA-2 and MONALEESA-2) and the larger body of consistent
evidence generated across trials
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MONARCH-3: Summary and Context
Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
Effect size was consistent in de novo and recurrent metastatic disease
Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
{ + Lack of statistical significance in this final OS analysis may be viewed as a limitation, but it is
1 important to consider the clinical relevance of the absolute effect size in the context of the
1
1
1
limitations of the study design (smaller sample size than that in PALOMA-2 and MONALEESA-2) and
the larger body of cot
tent evidence generated across
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Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS
(ITT population: 13.1 mo; subgroup with visceral disease: 14.9 mo) in patients with HR+, HER2- ABC;
however, statistical significance was not reached
Consistent OS effect size was seen across all subgroups, notably in patients with:
— Potential to have more comorbidities such as the elderly and those with an ECOG PS score of 1
— Bone-only and visceral disease (in contrast, no numerical effect was observed in patients with liver
metastases with the addition of ribociclib to letrozole in MONALEESA-2)
Effect size was consistent in de novo and recurrent metastatic disease
Effect of abemaciclib was largest in patients with prior Al therapy and those with PgR- disease
MONARCH-3 OS data are consistent with the findings in MONARCH-2, where the addition of abemaciclib to
fulvestrant resulted in a larger OS effect in patients with primary endocrine resistance
{ + Lack of statistical significance in this final OS analysis may be viewed as a limitation, but it is
1 important to consider the clinical relevance of the absolute effect size in the context of the
1
1
1
limitations of the study design (smaller sample size than that in PALOMA-2 and MONALEESA-2) and
the larger body of cot
tent evidence generated across
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Case 1 Discussion and Recommendation:
for a Patient With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history
of invasive carcinoma of the breast (ductal), pT2N1,
grade 3, ER+, PgR-, HER2-
History: Mammogram/US showed a 2.9-cm mass + enlarged,
suspicious axillary LN
- Underwent lumpectomy > adjuvant chemotherapy (TC) >
breast RT > adjuvant Al
— Patient has a long-standing history of bipolar disorder, well
controlled on qu
‘Two years after starting Al develops right hip pain > bone scan
reveals lytic bone lesions
CT CIAPP also shows numerous liver and bone metastases
involving spine, hip, and ribs
Biopsy of the liver shows ER+, PgR-, HER2- carcinoma c/w breast
Blood work shows normal liver function studies
BRCA1/2-
Baseline EKG: QTo 575 ms
Let's Discuss
What treatment would be the best option
for this patient, and which factors should
be taken into consideration in determining
the best 1L therapy for her?
¥ Comorbidities (bipolar, current medication)
v Liver disease/function
Y PgR- tumor
v Tumor biology: endocrine resistance,
timing
Drug dosing (continuous vs intermittent)
Cardiac health (prolonged QT interval)
Drug-drug interactions (medications,
supplements)
Patient needs and preferences
Copyright © 2000-2024, Peerview
for a Patient With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history
of invasive carcinoma of the breast (ductal), pT2N1,
grade 3, ER+, PgR-, HER2-
History: Mammogram/US showed a 2.9-cm mass + enlarged,
suspicious axillary LN
- Underwent lumpectomy > adjuvant chemotherapy (TC) >
breast RT > adjuvant Al
— Patient has a long-standing history of bipolar disorder, well
controlled on qu
‘Two years after starting Al develops right hip pain > bone scan
reveals lytic bone lesions
CT CIAPP also shows numerous liver and bone metastases
involving spine, hip, and ribs
Biopsy of the liver shows ER+, PgR-, HER2- carcinoma c/w breast
Blood work shows normal liver function studies
BRCA1/2-
Baseline EKG: QTo 575 ms
Let's Discuss
What treatment would be the best option
for this patient, and which factors should
be taken into consideration in determining
the best 1L therapy for her?
¥ Comorbidities (bipolar, current medication)
v Liver disease/function
Y PgR- tumor
v Tumor biology: endocrine resistance,
timing
Drug dosing (continuous vs intermittent)
Cardiac health (prolonged QT interval)
Drug-drug interactions (medications,
supplements)
Patient needs and preferences
Copyright © 2000-2024, Peerview
Case 1 Variations: What If? 1L Therapy for a Patient im
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
|
+ Hig
sug
-1
Let's Discuss
IA 68-year-old woman is diagnosed with v What treatment would be best if
HR+, HER2- MBC o the patient had de novo
metastatic disease?
+ Baseline EKG: QTc 575 ms
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With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
|
+ Hig
sug
-1
Let's Discuss
IA 68-year-old woman is diagnosed with v What treatment would be best if
HR+, HER2- MBC o the patient had de novo
metastatic disease?
+ Baseline EKG: QTc 575 ms
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Case 1 Variations: What If? 1L Therapy for a Patient im
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
‘
+ Hig
sug
7 Let’s Discuss
la 68-year-old woman is diagnosed with Y” What treatment would be best if
HR+, HER2- MBC in the patient was younger and
premenopausal?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
‘
+ Hig
sug
7 Let’s Discuss
la 68-year-old woman is diagnosed with Y” What treatment would be best if
HR+, HER2- MBC in the patient was younger and
premenopausal?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Case 1 Variations: What If? 1L Therapy for a Patient im
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history.of invasive
Let's Discuss
| A 68-year-old woman is diagnosed with 7 Weliten era as
a L I N $ e 7
HR+, HER2- MBC E best if the patient had brain
metastases or skull-based or
dural lesions?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history.of invasive
Let's Discuss
| A 68-year-old woman is diagnosed with 7 Weliten era as
a L I N $ e 7
HR+, HER2- MBC E best if the patient had brain
metastases or skull-based or
dural lesions?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Case 1 Variations: What If? 1L Therapy for a Patient im
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
\
+ Hig
sus
TER a Let’s Discuss
A 68-year-old woman is diagnosed with TT
{ HR+, HER2- MBC and comes to a clinic v What treatment would be
visit with the medical oncologist to |, best if the patient had bone-
discuss options for 1L therapy only disease?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
\
+ Hig
sus
TER a Let’s Discuss
A 68-year-old woman is diagnosed with TT
{ HR+, HER2- MBC and comes to a clinic v What treatment would be
visit with the medical oncologist to |, best if the patient had bone-
discuss options for 1L therapy only disease?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Case 1 Variations: What If? 1L Therapy for a Patient im
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
\
+ Hig
sus
A Let's Discuss
lA 68-year-old woman is diagnosed with
{ HR+, HER2- MBC and comes to a clinic v What treatment would be
- mw Visit with the medical oncologist to best if the patient had abnormal
discuss options for 1L therapy LFTs?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright O 2000-2024, PeerView
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
\
+ Hig
sus
A Let's Discuss
lA 68-year-old woman is diagnosed with
{ HR+, HER2- MBC and comes to a clinic v What treatment would be
- mw Visit with the medical oncologist to best if the patient had abnormal
discuss options for 1L therapy LFTs?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright O 2000-2024, PeerView
Case 1 Variations: What If? 1L Therapy for a Patient om
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
Let's Discuss
A 68-year-old woman is diagnosed with Y What treatment would be
{ HR+, HER2- MBC and comes to a clinic best if the patient had
visit with the medical oncologist to |, 5 i fr
discuss options for 1L therapy expen enced di jarrhea from
prior medications?
+ Baseline EKG: QTc 575 ms
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
With HR+, HER2- MBC
A 68-year-old postmenopausal woman has a history of invasive
Let's Discuss
A 68-year-old woman is diagnosed with Y What treatment would be
{ HR+, HER2- MBC and comes to a clinic best if the patient had
visit with the medical oncologist to |, 5 i fr
discuss options for 1L therapy expen enced di jarrhea from
prior medications?
+ Baseline EKG: QTc 575 ms
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Introduction to Case 2: Patient With HR+, HER2- MBC Tm
Progressing on 1L Therapy
A 68-year-old postmenopausal woman is diagnosed with HR+, HER2- MBC
Receives first-line CDK4/6i (palbociclib) + ET, but after 18 months develops
asymptomatic progression in bone and 1.5-cm new liver lesions
ctDNA testing reveals no ESR1 mutations or PIK3CA/AKT/PTEN pathway
alterations
No germline BRCA1/2 mutations
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Progressing on 1L Therapy
A 68-year-old postmenopausal woman is diagnosed with HR+, HER2- MBC
Receives first-line CDK4/6i (palbociclib) + ET, but after 18 months develops
asymptomatic progression in bone and 1.5-cm new liver lesions
ctDNA testing reveals no ESR1 mutations or PIK3CA/AKT/PTEN pathway
alterations
No germline BRCA1/2 mutations
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
HR+, HER2- Advanced Breast Cancer After First-Line
CDKi Progression (Randomized Data)
Drug Trial Prior CDKi, % mPFS, mo
Amcenestrant AMEERA-3? 80 3.6 (independent of ESR1 mutation)
Camizestrant SERENA-2! (phase 2) 9.2 (150 mg and ESR1 mutation)
com 72 M
Vepdegestrant VERITAC-2 (phase 2) 5.5 (ESR1 mutation)
Venetoclax VERONICA’ (phase 2) du 2.69
Ribociclib MAINTAIN® (phase 2) 100 53
Palbociclib PACE® (phase 2) 100 46
Palbociclib PALMIRA! (phase 2 400 49
asertib CAPItello-291" (phase 3) 7.3 (pathway altered)
Alpelisib BYLieve'? (nonrandomized) 7.3 (cohort A)
1. Marin. Gin Oncol Published one March 27, 2024. doi:10 12001100 23.01500. 2. Tolanay 8 a a. J Cin Oncol 2023,41:4014-4024,
3. Bara À Furure Oncot2019;18:3200 3218. 4. Olvera lot al. SABCS 2022. Abstract GS3-02 5, Goetz Metal Ann Oncol 2023:34:1141-1151
8. Huriz $ et al SABCS 2022. Abstract 683.09, 7. Lindeman GJ etal. Cin Concer Ros. 2022.28: 3258-367. 8, Kalsky K tal. J Clin Oncol 2023:41 4004-4013.
9. Mayer EL et al. J Cin Oncol Publishes onine March 2, 2024 dot 10,12001JC0 23.01940. 10.Cussac AL et a Anal Oncol 2018,30'5s (supp abst VA). 7
11. Tumer NC et al. N Engi J Mod. 2023;388:2058-2070. 12. Rugo HS el al. Lancet Oncol. 2021:22486498. PeerView.com
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CDKi Progression (Randomized Data)
Drug Trial Prior CDKi, % mPFS, mo
Amcenestrant AMEERA-3? 80 3.6 (independent of ESR1 mutation)
Camizestrant SERENA-2! (phase 2) 9.2 (150 mg and ESR1 mutation)
com 72 M
Vepdegestrant VERITAC-2 (phase 2) 5.5 (ESR1 mutation)
Venetoclax VERONICA’ (phase 2) du 2.69
Ribociclib MAINTAIN® (phase 2) 100 53
Palbociclib PACE® (phase 2) 100 46
Palbociclib PALMIRA! (phase 2 400 49
asertib CAPItello-291" (phase 3) 7.3 (pathway altered)
Alpelisib BYLieve'? (nonrandomized) 7.3 (cohort A)
1. Marin. Gin Oncol Published one March 27, 2024. doi:10 12001100 23.01500. 2. Tolanay 8 a a. J Cin Oncol 2023,41:4014-4024,
3. Bara À Furure Oncot2019;18:3200 3218. 4. Olvera lot al. SABCS 2022. Abstract GS3-02 5, Goetz Metal Ann Oncol 2023:34:1141-1151
8. Huriz $ et al SABCS 2022. Abstract 683.09, 7. Lindeman GJ etal. Cin Concer Ros. 2022.28: 3258-367. 8, Kalsky K tal. J Clin Oncol 2023:41 4004-4013.
9. Mayer EL et al. J Cin Oncol Publishes onine March 2, 2024 dot 10,12001JC0 23.01940. 10.Cussac AL et a Anal Oncol 2018,30'5s (supp abst VA). 7
11. Tumer NC et al. N Engi J Mod. 2023;388:2058-2070. 12. Rugo HS el al. Lancet Oncol. 2021:22486498. PeerView.com
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Fulvestrant and Everolimus Efficacy After CDK4/6
Inhibitor’
PFS and OS in patients treated with everolimus and fulvestrant in the whole population
and according to previous palbociclib treatment duration
(3)
1. Vassour A tal. Oncogene, 2028:43:1214-1222 PeerView.com
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Inhibitor’
PFS and OS in patients treated with everolimus and fulvestrant in the whole population
and according to previous palbociclib treatment duration
(3)
1. Vassour A tal. Oncogene, 2028:43:1214-1222 PeerView.com
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What About 2L CDK4/6i Post-Progression
on 1L CDKi?1-3
MAINTAIN PACE PALMIRA
Patients, n 120 166 198
First-line CDK4/6i Palbociclib (84%) Palbociclib (90%) Palbociclib (100%)
First-line CDK4/6i >12 mo, % 67 75 86
Fulvestrant (83%) or Fulvestrant (90%) or
Endocrine therapy Fulvestrant (100%)
exemestane
“Continuation” CDK4/6i Ribociclib Palbociclib Palbociclib
letrozole
PFS ET only, mo
PFS fulvestrant + CDK4/6i, mo
Different studies, designs, study populations, and subgroup definitions
1. Kalinsky et al. J Glin Oncol 2023:41:4004-4013. 2. Mayer EL etal. SABCS 2022. Abstract GS3-06. 3. Liambart-Cussac A et al. ASCO 2023. Abstract 1001. PeerView.com
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on 1L CDKi?1-3
MAINTAIN PACE PALMIRA
Patients, n 120 166 198
First-line CDK4/6i Palbociclib (84%) Palbociclib (90%) Palbociclib (100%)
First-line CDK4/6i >12 mo, % 67 75 86
Fulvestrant (83%) or Fulvestrant (90%) or
Endocrine therapy Fulvestrant (100%)
exemestane
“Continuation” CDK4/6i Ribociclib Palbociclib Palbociclib
letrozole
PFS ET only, mo
PFS fulvestrant + CDK4/6i, mo
Different studies, designs, study populations, and subgroup definitions
1. Kalinsky et al. J Glin Oncol 2023:41:4004-4013. 2. Mayer EL etal. SABCS 2022. Abstract GS3-06. 3. Liambart-Cussac A et al. ASCO 2023. Abstract 1001. PeerView.com
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Other Key Studies Assessing Continuation
of CDK4/6 Inhibition Beyond Progression
postMONARCH (NCT05169567)'
Does abemaciclib + fulvestrant improve outcomes
after adjuvant or first-line CDK4/6i + ET?
EMBER-3 (NCT04975308)?
How well does imlunestrant + abemaciclib work
compared with standard hormone therapy?
HR#/HER2- MBC pre-
and postmenopausal HR+, HERZ- locally 1:1:1 Imlunestrant +
adults (women and men) ABC or MBC abemaciclib
= Prior heresy Abemaciclib + fulvestrant + Iffemale,
— Advanced setting: postmenopausal Ferner)
+ ECOG PS Dor1
+ Measurable disease
(per RECIST v1.1)
Disease progression fulvestrant
on CDK4/6i plus an Al
as initial therapy, or
Imlunestrant
Placebo + fulvestrant
= Adjuvant setting: an + Adequate organ
Disease recurrence on function
or after CDK4/6i + ET
(N = 350)
Completed Accrual,
results pending
Reported ASCO24
1. mis: einicalrats govisudy INCTOS189567. 2. htps:icnicalsials govstudy/NCTOAS76308. PeerView.com
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of CDK4/6 Inhibition Beyond Progression
postMONARCH (NCT05169567)'
Does abemaciclib + fulvestrant improve outcomes
after adjuvant or first-line CDK4/6i + ET?
EMBER-3 (NCT04975308)?
How well does imlunestrant + abemaciclib work
compared with standard hormone therapy?
HR#/HER2- MBC pre-
and postmenopausal HR+, HERZ- locally 1:1:1 Imlunestrant +
adults (women and men) ABC or MBC abemaciclib
= Prior heresy Abemaciclib + fulvestrant + Iffemale,
— Advanced setting: postmenopausal Ferner)
+ ECOG PS Dor1
+ Measurable disease
(per RECIST v1.1)
Disease progression fulvestrant
on CDK4/6i plus an Al
as initial therapy, or
Imlunestrant
Placebo + fulvestrant
= Adjuvant setting: an + Adequate organ
Disease recurrence on function
or after CDK4/6i + ET
(N = 350)
Completed Accrual,
results pending
Reported ASCO24
1. mis: einicalrats govisudy INCTOS189567. 2. htps:icnicalsials govstudy/NCTOAS76308. PeerView.com
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postMONARCH: Abemaciclib + Fulvestrant
Following Progression on Prior CDK4/6i + ET!
Primary Analysi:
Abemaciclib Improved Investigator-Assessed PFS.
Placebo
+Fulvestrant
80
= Events, n 141
ae Emo PES rete Median (95% C),mo 6016686) — §.3(8756)
oe HR (05% Ci) 073 (057.085)
= 4 la oe
30
= Abemacicib + fulvestrant
10 u
à Placebo + fulvestrant
2
Time, mo
oat Rink
Behe 122 m “0 a A a 2 o
Poor 186 m E = 7 7 3 °
Abemaciclib led to 27% reduction in the risk of developing PFS event.
1. Kalinsty Ket al. ASCO 2024. Abstract LBA1001 PeerView.com
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Following Progression on Prior CDK4/6i + ET!
Primary Analysi:
Abemaciclib Improved Investigator-Assessed PFS.
Placebo
+Fulvestrant
80
= Events, n 141
ae Emo PES rete Median (95% C),mo 6016686) — §.3(8756)
oe HR (05% Ci) 073 (057.085)
= 4 la oe
30
= Abemacicib + fulvestrant
10 u
à Placebo + fulvestrant
2
Time, mo
oat Rink
Behe 122 m “0 a A a 2 o
Poor 186 m E = 7 7 3 °
Abemaciclib led to 27% reduction in the risk of developing PFS event.
1. Kalinsty Ket al. ASCO 2024. Abstract LBA1001 PeerView.com
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postMONARCH: Abemaciclib + Fulvestrant
Following Progression on Prior CDK4/6i + ET!
Investigator-Assessed PFS by Subgroup: Consistent Effect Across Subgroups
PR status
Neza
"ASC 212 me o ter adorar COX
ABC <12 moo ng port COKE
Pier COX
bees
1. Kalinsty K et al. ASCO 2024. Abstract LBA1001.
PeerView.com/AGR827
m
201
s
2
a
we
=
zu
2
04
08 08 101218 10
HR (8 CI)
070708)
o78 108407)
083 (047097)
0711055099
020 (044-120)
020 (041-188)
072 (084098)
O7 yoaes.%6)
sr (ase)
053 (034083)
083 044081)
0781056108)
9511028085)
O7 (00102)
07510709)
0731048128)
o7o(osea9s)
020 (060120)
062 (044098)
101 067-151)
PeerView.com
Copyright © 2000-2024, Peerview
Following Progression on Prior CDK4/6i + ET!
Investigator-Assessed PFS by Subgroup: Consistent Effect Across Subgroups
PR status
Neza
"ASC 212 me o ter adorar COX
ABC <12 moo ng port COKE
Pier COX
bees
1. Kalinsty K et al. ASCO 2024. Abstract LBA1001.
PeerView.com/AGR827
m
201
s
2
a
we
=
zu
2
04
08 08 101218 10
HR (8 CI)
070708)
o78 108407)
083 (047097)
0711055099
020 (044-120)
020 (041-188)
072 (084098)
O7 yoaes.%6)
sr (ase)
053 (034083)
083 044081)
0781056108)
9511028085)
O7 (00102)
07510709)
0731048128)
o7o(osea9s)
020 (060120)
062 (044098)
101 067-151)
PeerView.com
Copyright © 2000-2024, Peerview
postMONARCH: Abemaciclib + Fulvestrant
Following Progression on Prior CDK4/6i + ET!
Safety Consistent With Known Abemaci Profile
Abemaciclib + Fulvestrant (n= 181) Placebo + Fulvestrant (n = 185)
‘Grade 5 TRAES,n (%) 108) 0
Dose reduction due lo AE, n (%) 55 (30.0) 6.0)
Discontinuation due to AE, 1160) 0
TEAES, % Any Grade Grade 23 Any Grade Grado 23
Any 7 ES Ez 20
Dierhea 75 4 17 2
Neutropenia? a 25: 3 o
Anemia? 35 1 15 4
Fatigue? 33 3 23 1
Nausea ES 3 18 0
Abdominal pain? 24 2 16 0
Vomiting 20 2 6 o
Thrombocytopent 18 4 6 2
Decreased appa 18 1 7 0
Leukopenia® 18 8 3 o
AST increased 15 6 “ 2
ALT increased 13 4 10 2
arthralgia 12 1 12 1
(Creatinine increased " o 2 o
Cough " o 7 0
2 3 1
ites 3 1 o
+ one grade 5 TRAE of pneumona.
* Consobeted term Includes, wo febrile nuropenia (one grado 3. one grade 4. ne grado pulmonary embolism, «one grade 3, one grado LO. E
1. Kalnsky K et a. ASCO 2024. Abstract LBA 1001 PeerView.com
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Following Progression on Prior CDK4/6i + ET!
Safety Consistent With Known Abemaci Profile
Abemaciclib + Fulvestrant (n= 181) Placebo + Fulvestrant (n = 185)
‘Grade 5 TRAES,n (%) 108) 0
Dose reduction due lo AE, n (%) 55 (30.0) 6.0)
Discontinuation due to AE, 1160) 0
TEAES, % Any Grade Grade 23 Any Grade Grado 23
Any 7 ES Ez 20
Dierhea 75 4 17 2
Neutropenia? a 25: 3 o
Anemia? 35 1 15 4
Fatigue? 33 3 23 1
Nausea ES 3 18 0
Abdominal pain? 24 2 16 0
Vomiting 20 2 6 o
Thrombocytopent 18 4 6 2
Decreased appa 18 1 7 0
Leukopenia® 18 8 3 o
AST increased 15 6 “ 2
ALT increased 13 4 10 2
arthralgia 12 1 12 1
(Creatinine increased " o 2 o
Cough " o 7 0
2 3 1
ites 3 1 o
+ one grade 5 TRAE of pneumona.
* Consobeted term Includes, wo febrile nuropenia (one grado 3. one grade 4. ne grado pulmonary embolism, «one grade 3, one grado LO. E
1. Kalnsky K et a. ASCO 2024. Abstract LBA 1001 PeerView.com
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Case 2 Discussion and Recommendations: Patient With Tm
HR+, HER2- MBC Progressing on 1L Therapy
A 68-year-old postmenopausal woman is te Di
diagnosed with HR+, HER2- MBC Lets Discuss)
Y” What treatment is the best
+ Receives first-line CDK4/6i (palbociclib) + ET, but | Option for this patient and why?
after 18 months develops asymptomatic
progression in bone and 1.5-cm new liver lesions | What are the implications of the
+» ctDNA testing reveals no ESR1 mutations or postMONARCH trial results
PIK3CA/AKT/PTEN pathway alterations presented at ASCO 2024?
+ No germline BRCA 1/2 mutations
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
HR+, HER2- MBC Progressing on 1L Therapy
A 68-year-old postmenopausal woman is te Di
diagnosed with HR+, HER2- MBC Lets Discuss)
Y” What treatment is the best
+ Receives first-line CDK4/6i (palbociclib) + ET, but | Option for this patient and why?
after 18 months develops asymptomatic
progression in bone and 1.5-cm new liver lesions | What are the implications of the
+» ctDNA testing reveals no ESR1 mutations or postMONARCH trial results
PIK3CA/AKT/PTEN pathway alterations presented at ASCO 2024?
+ No germline BRCA 1/2 mutations
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Key Takeaways
e Important differences do exist among the CDK4/6 inhibitors > essential to
individualize therapy and consider all the relevant tumor-/disease-, treatment-, and
patient-related factors in selecting the best CDK4/6 inhibitor-based regimen for
patients with HR+, HER2- MBC
Important to implement effective communication, care coordination, and
collaboration among the multidisciplinary team, as well as engagement of patients
in shared decision-making
PeerView.com
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e Important differences do exist among the CDK4/6 inhibitors > essential to
individualize therapy and consider all the relevant tumor-/disease-, treatment-, and
patient-related factors in selecting the best CDK4/6 inhibitor-based regimen for
patients with HR+, HER2- MBC
Important to implement effective communication, care coordination, and
collaboration among the multidisciplinary team, as well as engagement of patients
in shared decision-making
PeerView.com
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MAKING PRECISION DECISIONS IN HIGH-RISK HR+, HER2- METASTATIC BREAST CANCER | OUTLINE
PART 1
PART 2
Making Multifactorial Clinical Decisions
About the Selection and Use of First-line
CDK4/6 Inhibitors in High-Risk
HR+, HER2- MBC
Managing Adverse Events, Improving
Adherence/Persistence, and Maximizing
Treatment Benefits of CDK4/6 Inhibitors
PART 1
PART 2
Making Multifactorial Clinical Decisions
About the Selection and Use of First-line
CDK4/6 Inhibitors in High-Risk
HR+, HER2- MBC
Managing Adverse Events, Improving
Adherence/Persistence, and Maximizing
Treatment Benefits of CDK4/6 Inhibitors
Case 1 Continues: Patient With HR+, HER2- MBC
Develops Diarrhea on 1L CDK4/6i Therapy
A 68-year-old postmenopausal woman has a history of invasive carcinoma of the breast (ductal),
pT2N1, grade 3, ER+, PgR-, HER2-
History: Mammogram/US showed a 2.9-cm mass + enlarged, suspicious axilary LN
lumpectomy > adjuvant chemotherapy (TC) > breast RT > adjuvant Al
ding history of bipolar disorder, well controlled on quetiapine
lps right hip pain > bone scan reveats Itc bone lesions
CT CIAP also shows numerous liver and bone metastases involving spine, hip, and ribs
Biopsy ofthe Iver shows ER+, PgR-. HERZ- carcinoma ch breast
Blood work shows normal iver function studies
BRCA1/2
Baseline EKG: QTc 575 ms
Receives abemaciclib + ET and responds well but develops grade 2 diarrhea
Reports that she took a break from therapy because of travel and the diarrhea improved; restarts therapy
but now the symptoms worsen again
PeerView.com/AGR827 Copyright O 2000-2024, Peerview
Develops Diarrhea on 1L CDK4/6i Therapy
A 68-year-old postmenopausal woman has a history of invasive carcinoma of the breast (ductal),
pT2N1, grade 3, ER+, PgR-, HER2-
History: Mammogram/US showed a 2.9-cm mass + enlarged, suspicious axilary LN
lumpectomy > adjuvant chemotherapy (TC) > breast RT > adjuvant Al
ding history of bipolar disorder, well controlled on quetiapine
lps right hip pain > bone scan reveats Itc bone lesions
CT CIAP also shows numerous liver and bone metastases involving spine, hip, and ribs
Biopsy ofthe Iver shows ER+, PgR-. HERZ- carcinoma ch breast
Blood work shows normal iver function studies
BRCA1/2
Baseline EKG: QTc 575 ms
Receives abemaciclib + ET and responds well but develops grade 2 diarrhea
Reports that she took a break from therapy because of travel and the diarrhea improved; restarts therapy
but now the symptoms worsen again
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Differences in AE Profiles Among
the CDK4/6 Inhibitors‘
Palbociclib Ribociclib
(PALOM: (MONARCH 3) (MONALEESA-2)
Common AE, % All Grades Grade 3/4 All Grades Grade 3/4 All Grades Grade 3/4
Neutropenia 66.4 43.7 23.8 743 59.3
Fatigue 18 413 18 36.5 24
Diarrhea 14 823 9.5 35.0 12
Nausea 02 413 12 51.5 24
Anemia 241 54 31.5 70 18.6 12
Vomiting 15.5 05 30.3 15 29.3 36
Te prolongation NR NR NR NR 27
ALT increase 146 27 22.0 80 20.4
AST increase 14.4 29 21.4 49
LEFT
EKG
coc a a
1. Finn RS et al N Eng! J Mod. 2016:376:1925-1998.2. Hortobagyi GN otal N Engl J Med. 2016;375:1738-1748, 8, Johnston 8 et al. NPY Breast Cancer 202955. PeerVieW.com
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the CDK4/6 Inhibitors‘
Palbociclib Ribociclib
(PALOM: (MONARCH 3) (MONALEESA-2)
Common AE, % All Grades Grade 3/4 All Grades Grade 3/4 All Grades Grade 3/4
Neutropenia 66.4 43.7 23.8 743 59.3
Fatigue 18 413 18 36.5 24
Diarrhea 14 823 9.5 35.0 12
Nausea 02 413 12 51.5 24
Anemia 241 54 31.5 70 18.6 12
Vomiting 15.5 05 30.3 15 29.3 36
Te prolongation NR NR NR NR 27
ALT increase 146 27 22.0 80 20.4
AST increase 14.4 29 21.4 49
LEFT
EKG
coc a a
1. Finn RS et al N Eng! J Mod. 2016:376:1925-1998.2. Hortobagyi GN otal N Engl J Med. 2016;375:1738-1748, 8, Johnston 8 et al. NPY Breast Cancer 202955. PeerVieW.com
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MONARCH-2 and MONARCH-3: No Impact of Dose
Reductions on Efficacy in HR+, HER2- MBC"
In the abemaciclib arms of MONARCH-2 and -3, 189 (42.9%) and 142 (43.4%) patients had dose reductions due to AEs
Most frequent AEs accounting for 210% of dose reductions were grade 2 or 3 diarthea (14%-19%) and grade 23 neutropenia
(10%-13%)
In both studies, there was no difference in PFS when the dose was reduced to 100 mg or 50 mg at any point in the treatment
‘compared with being treated at the 150-mg dose
MONARCH-2
100 mg abemaciclib + fulvestrant vs 150 mg (reference) 1.03 (0.68-1.57)
50 mg abemaciclib + fulvestrant vs 150 mg (reference) 0.92 (0.50-1.71)
MONARCH-3
100 mg abemaciclib + NSAI vs 150 mg (reference) 0.76 (0.47-1.25)
0.99 (0.51-1.90)
50 mg abemaciclib + NSAI vs 150 mg (reference)
4 0 1 2 3
+<—_— —
Favors lower dose Favors reference ), |;
PeerView.com
1. Rugo HS et al. Oncologist 2021;26:053-066.
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Reductions on Efficacy in HR+, HER2- MBC"
In the abemaciclib arms of MONARCH-2 and -3, 189 (42.9%) and 142 (43.4%) patients had dose reductions due to AEs
Most frequent AEs accounting for 210% of dose reductions were grade 2 or 3 diarthea (14%-19%) and grade 23 neutropenia
(10%-13%)
In both studies, there was no difference in PFS when the dose was reduced to 100 mg or 50 mg at any point in the treatment
‘compared with being treated at the 150-mg dose
MONARCH-2
100 mg abemaciclib + fulvestrant vs 150 mg (reference) 1.03 (0.68-1.57)
50 mg abemaciclib + fulvestrant vs 150 mg (reference) 0.92 (0.50-1.71)
MONARCH-3
100 mg abemaciclib + NSAI vs 150 mg (reference) 0.76 (0.47-1.25)
0.99 (0.51-1.90)
50 mg abemaciclib + NSAI vs 150 mg (reference)
4 0 1 2 3
+<—_— —
Favors lower dose Favors reference ), |;
PeerView.com
1. Rugo HS et al. Oncologist 2021;26:053-066.
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
monarchE: Efficacy of Adjuvant Abemaciclib Not
Compromised by Dose Reductions in High-Risk EBC‘
+ Dose reductions due to AEs occurred in 43.4% of patients treated with adjuvant abemacicli
+ Dose modifications effectively managed AEs and retained more patients on treatment
+ Based on multiple analyses, efficacy of adjuvant abemaciclib was not compromised by dose reductions
IDFS by RDI Subgroup in Patients Treated With Abemaciclib Time-dependent Cox PH model for the impact of
pe dose reductions on IDFS and DRFS
56%
1 65-95% Assessment of Efficacy Staying
en A Full Dose vs Boing Reduced
i Efficacy Endpoint 10 a Lower Dose
Reo
"| muunsome ZoNa ati dior (5% ch
SE | Mimi CC CR OT CR BHC
El En 0905 0922
zs] men min mann) MON Gamasemacier 7 (@727-1.125) (0740-4148)
In intentare
nan BRO BIZ mama 094 0954
population PRES 07421199) (0751-4212)
00% Mn Mama) 2707.00
° ‘tes [777 os
DE mm nn mn m m nn (071861.125) (0782-4150)
Time (months
“SS eo eee 0 om w me ES Ai m
Zu mm wo mm 2 9 usa] reta
Ze um mm MI MS Ai M M 0
Hazard ratio (8% CI) was astimatod using a Sme-dopandeet Cox proprtenal hazards model io ssoss ro impact of does levels over tine on IDFS and ORFS.» Aue by confounding baesine
{actors ndvidualy associatod wih fs of rcurenca, including age, srafcaton acors, kay disease charac, and pro-oxising eo-mariiies. "Cohor 1 included patients wih 24 positive
palhooge ALNS or 1:3 postive ALNS pls tumor siz 25cm andor lumor grado 3 Re
1 Goetz MP et al. NP Breast Cancer. 2024; 10: 34, Published onine 2024 Apr 25. di: 10.109644 1523-024.00638-1 PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Compromised by Dose Reductions in High-Risk EBC‘
+ Dose reductions due to AEs occurred in 43.4% of patients treated with adjuvant abemacicli
+ Dose modifications effectively managed AEs and retained more patients on treatment
+ Based on multiple analyses, efficacy of adjuvant abemaciclib was not compromised by dose reductions
IDFS by RDI Subgroup in Patients Treated With Abemaciclib Time-dependent Cox PH model for the impact of
pe dose reductions on IDFS and DRFS
56%
1 65-95% Assessment of Efficacy Staying
en A Full Dose vs Boing Reduced
i Efficacy Endpoint 10 a Lower Dose
Reo
"| muunsome ZoNa ati dior (5% ch
SE | Mimi CC CR OT CR BHC
El En 0905 0922
zs] men min mann) MON Gamasemacier 7 (@727-1.125) (0740-4148)
In intentare
nan BRO BIZ mama 094 0954
population PRES 07421199) (0751-4212)
00% Mn Mama) 2707.00
° ‘tes [777 os
DE mm nn mn m m nn (071861.125) (0782-4150)
Time (months
“SS eo eee 0 om w me ES Ai m
Zu mm wo mm 2 9 usa] reta
Ze um mm MI MS Ai M M 0
Hazard ratio (8% CI) was astimatod using a Sme-dopandeet Cox proprtenal hazards model io ssoss ro impact of does levels over tine on IDFS and ORFS.» Aue by confounding baesine
{actors ndvidualy associatod wih fs of rcurenca, including age, srafcaton acors, kay disease charac, and pro-oxising eo-mariiies. "Cohor 1 included patients wih 24 positive
palhooge ALNS or 1:3 postive ALNS pls tumor siz 25cm andor lumor grado 3 Re
1 Goetz MP et al. NP Breast Cancer. 2024; 10: 34, Published onine 2024 Apr 25. di: 10.109644 1523-024.00638-1 PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Oncologist and Patient Preferences for Attributes of
CDK4/6 Inhibitors in HR+ HER2- MBC‘
+ In a preference study conducted in the
United States focusing on safety (but not
efficacy), attributes influencing treatment 20 — Patents
choice, the risk of diarrhea, and grade 3 is mn
or 4 neutropenia were key drivers of
ann Per for on Ir
oncologists and patients wit ~ \ Su
os yy
— Considered substantially more
important than the risk of dose
reduction for adverse events
Mean Preference Weights
+ Oncologists also considered the need for 4p
electrocardiogram monitoring to be SEE SSS EEE LE SES CES See
important e
Risk of
+ Dosing frequency was not a key factor in escalón” ordiaines APTA yostring ofNeutropeta REGIME" Grade
patient and oncologist preferences
1. Macuais MC eta. Patent Profor Adheranco. 2020;14:2201-2216. PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
CDK4/6 Inhibitors in HR+ HER2- MBC‘
+ In a preference study conducted in the
United States focusing on safety (but not
efficacy), attributes influencing treatment 20 — Patents
choice, the risk of diarrhea, and grade 3 is mn
or 4 neutropenia were key drivers of
ann Per for on Ir
oncologists and patients wit ~ \ Su
os yy
— Considered substantially more
important than the risk of dose
reduction for adverse events
Mean Preference Weights
+ Oncologists also considered the need for 4p
electrocardiogram monitoring to be SEE SSS EEE LE SES CES See
important e
Risk of
+ Dosing frequency was not a key factor in escalón” ordiaines APTA yostring ofNeutropeta REGIME" Grade
patient and oncologist preferences
1. Macuais MC eta. Patent Profor Adheranco. 2020;14:2201-2216. PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Principles of Prophylaxis and Management of Diarrhea
Be proactive about patient education and communication
+ Ensure patients have an OTC antidiarrheal (eg, loperamide) on hand before starting therapy
+ Discuss recommended dietary changes
+ Communicate about the importance on staying on therapy, the potential for dose reductions, and that
dose modifications can help to improve tolerability without reducing treatment benefits
Implement strategies for diarrhea management to keep patients on treatment
+ Atthe first sign of loose stools, instruct patients to immediately start an antidiarrheal, increase fluids, and
notify your office
+ Follow up after 24 hours: if diarrhea has not resolved to grade <1, suspend abemaciclib until resolution
If necessary, reduce the dose
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Be proactive about patient education and communication
+ Ensure patients have an OTC antidiarrheal (eg, loperamide) on hand before starting therapy
+ Discuss recommended dietary changes
+ Communicate about the importance on staying on therapy, the potential for dose reductions, and that
dose modifications can help to improve tolerability without reducing treatment benefits
Implement strategies for diarrhea management to keep patients on treatment
+ Atthe first sign of loose stools, instruct patients to immediately start an antidiarrheal, increase fluids, and
notify your office
+ Follow up after 24 hours: if diarrhea has not resolved to grade <1, suspend abemaciclib until resolution
If necessary, reduce the dose
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Abemaciclib Dosing Recommendations
and Modifications
+ Start with the recommended starting dose, not with a reduced dose
* If dose reduction is necessary, reduce the abemaciclib dose by 50 mg at a time; discontinue treatment for
patients unable to tolerate 50 mg twice daily
In Combination With
Fulvestrant, Tamoxifen, or an Al ingle Agent
Recommended starting dose 150 mg twice daily 200 mg twice daily
4st dose reduction 100 mg twice daily 150 mg twice daily
2nd dose reduction 50 mg twice daily 100 mg twice daily
3rd dose reduction Not applicable 50 mg twice daily
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
and Modifications
+ Start with the recommended starting dose, not with a reduced dose
* If dose reduction is necessary, reduce the abemaciclib dose by 50 mg at a time; discontinue treatment for
patients unable to tolerate 50 mg twice daily
In Combination With
Fulvestrant, Tamoxifen, or an Al ingle Agent
Recommended starting dose 150 mg twice daily 200 mg twice daily
4st dose reduction 100 mg twice daily 150 mg twice daily
2nd dose reduction 50 mg twice daily 100 mg twice daily
3rd dose reduction Not applicable 50 mg twice daily
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Algorithm for Management of Diarrhea’
in of Loose Stools
Start antidiarrheal agents (eg, loperamidk
ease intake of oral fluids
Grade 4
Grade 1 Grade 2 Life-threatening
Increase of <4 stools Increase of 4-6 stools Increase of 27 stools densequencestngent
per day over baseline per day over baseline per day over baseline Intervention Hosted
Suspend dose until toxicity sy
resolves to grade <1 | ‘Suspend dose until toxicity resolves to grade $1 |
No dose modification
— | | —
+. Adapted tom Rugo HS ot al. Oncologist. 2021,26.053-065. PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
in of Loose Stools
Start antidiarrheal agents (eg, loperamidk
ease intake of oral fluids
Grade 4
Grade 1 Grade 2 Life-threatening
Increase of <4 stools Increase of 4-6 stools Increase of 27 stools densequencestngent
per day over baseline per day over baseline per day over baseline Intervention Hosted
Suspend dose until toxicity sy
resolves to grade <1 | ‘Suspend dose until toxicity resolves to grade $1 |
No dose modification
— | | —
+. Adapted tom Rugo HS ot al. Oncologist. 2021,26.053-065. PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Case 1 Discussion and Recommendations: Patient With m
HR+, HER2- MBC Develops Diarrhea on 1L CDK4/6i
A 68-year-old postmenopausal woman has a history of invasive
carcinoma of the breast (ductal), pT2N1, grade 3, ER+,
PgR-, HER2-
Let’s Discuss
Y” How to successfully manage the
diarrhea?
Y” When to consider dose
+ Receives abemaciclib + ET and responds well but CGS
develops grade 2 diarrhea Y How to optimize adherence and
+ Reports that she took a break from therapy because of persistence?
travel and the diarrhea improved; restarts therapy but
now the symptoms worsen again
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
HR+, HER2- MBC Develops Diarrhea on 1L CDK4/6i
A 68-year-old postmenopausal woman has a history of invasive
carcinoma of the breast (ductal), pT2N1, grade 3, ER+,
PgR-, HER2-
Let’s Discuss
Y” How to successfully manage the
diarrhea?
Y” When to consider dose
+ Receives abemaciclib + ET and responds well but CGS
develops grade 2 diarrhea Y How to optimize adherence and
+ Reports that she took a break from therapy because of persistence?
travel and the diarrhea improved; restarts therapy but
now the symptoms worsen again
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Case 1 Variations: What if the Patient Develops
Neutropenia? Management of Hematologic AEs’
+ Blood tests for CBCs should be monitored prior to the start of therapy, every 2 weeks for the
first 2 months, monthly for the next 2 months, and as clinically indicated
Hematologic Tox
Recurrent grade 3
Grade 3
‘Suspend until toxicity resolves to grade <2 |
Reduce to the next lower
dose
PeerView.com
Grade 1-2
No dose reduction required
No dose modification
required
1. Rugo HS otal. Oncologist 2021:26.083.065
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Neutropenia? Management of Hematologic AEs’
+ Blood tests for CBCs should be monitored prior to the start of therapy, every 2 weeks for the
first 2 months, monthly for the next 2 months, and as clinically indicated
Hematologic Tox
Recurrent grade 3
Grade 3
‘Suspend until toxicity resolves to grade <2 |
Reduce to the next lower
dose
PeerView.com
Grade 1-2
No dose reduction required
No dose modification
required
1. Rugo HS otal. Oncologist 2021:26.083.065
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Case 1 Variations: What if the Patient Develops ILD/Pneumonitis?
Strategies for Management of Pulmonary AEs‘
ILD and Pneumonitis
Recurrent grade 3 or
Grade 1 Grade 2 grade 4
Asymptomatic ‘Symptomatic Severe symptomatic/
life-threatening
Dose interruption unt
recovery to grade
No dose interruption or
eerie Resume at next lower dose
1.Rugo HS tal. Oncologist 2021:26.053-066 PeerView.com
BE Grace 2 our
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Strategies for Management of Pulmonary AEs‘
ILD and Pneumonitis
Recurrent grade 3 or
Grade 1 Grade 2 grade 4
Asymptomatic ‘Symptomatic Severe symptomatic/
life-threatening
Dose interruption unt
recovery to grade
No dose interruption or
eerie Resume at next lower dose
1.Rugo HS tal. Oncologist 2021:26.053-066 PeerView.com
BE Grace 2 our
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Case 1 Variations: What if the Patient Develops Liver Function
Abnormalities? Strategies for Management of Hepatobiliary AEs’
Hepatobiliary Toxicity
Parlorm LFTs before in
‘atthe
+ + + +
Grade 1 Grade 2 Grade 3 Grade 4
ŒULN to 3x ULN) (3 to 5x ULN) (25 to 20x ULN) (20x ULN)
Passing of urade ce dose. | cross | Dose interruption until recovery |
interruption until recovery
| aan grade 2 oS baseline grade
| æ | =
Resume at | Resume at next No dose Resume at next
seen] se. —
interruption || lower dose level
PeerView.com
No dose adjustment
required
1. Rugo HS otal, Oncologist 202126 053-066
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Abnormalities? Strategies for Management of Hepatobiliary AEs’
Hepatobiliary Toxicity
Parlorm LFTs before in
‘atthe
+ + + +
Grade 1 Grade 2 Grade 3 Grade 4
ŒULN to 3x ULN) (3 to 5x ULN) (25 to 20x ULN) (20x ULN)
Passing of urade ce dose. | cross | Dose interruption until recovery |
interruption until recovery
| aan grade 2 oS baseline grade
| æ | =
Resume at | Resume at next No dose Resume at next
seen] se. —
interruption || lower dose level
PeerView.com
No dose adjustment
required
1. Rugo HS otal, Oncologist 202126 053-066
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Case 1 Variations: What if the Patient Develops QT
Prolongation? Strategies for Management of Cardiac AEs‘
QT Prolongation
QT cF interval prolongation >500 ms
ECGs with QTcF >480 ms ECGs with QTcF >500 ms or >60 ms change from baseline
AND associated with any of the
following: Torsades de Pointes,
polymorphic ventricular
tachycardia, unexplained syncope,
or signs/symptoms of serious
arrhythmia
| Iter tint
481 m recurs
art osa un
resolves to <481 m:
| Tener nore | amenant sono
1. Rugo HS ot al, Oncologist 202126 053-066. PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Prolongation? Strategies for Management of Cardiac AEs‘
QT Prolongation
QT cF interval prolongation >500 ms
ECGs with QTcF >480 ms ECGs with QTcF >500 ms or >60 ms change from baseline
AND associated with any of the
following: Torsades de Pointes,
polymorphic ventricular
tachycardia, unexplained syncope,
or signs/symptoms of serious
arrhythmia
| Iter tint
481 m recurs
art osa un
resolves to <481 m:
| Tener nore | amenant sono
1. Rugo HS ot al, Oncologist 202126 053-066. PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Strategies for Optimizing Adherence and Persistence
+ Different methods available for measuring adherence: eg, oral therapy checklists, pill counts, pharmacy and administrative
records, medical record review and clinician reports, self or caregiver reports, electronic medication monitoring systems
(MEMS), web-based or mobile applications (apps)
+ Patient education, counseling, and shared
decision-making (SDM) are essential
+ To improve adherence and persistence, educate
patients on:
— Features of their disease and risk status, potential
More electronic tools emerging to allow for remote
monitoring and tracking of AEs and adherence/persistence
)
D PROS captured using web-based or mobile apps
in abemaciclib clinical trials
o) TEANADD: us hato nació AES, implications o nonadherence
application reacting to patient self-reported — Prophylactic measures that can be taken to be
observations > used for AE monitoring and PROS | Better prepared to address potential AEs
(eg, providing patients with a prescription for
antidiarrheal medication and suggesting having that
always at hand should an episode of diarrhea occur)
in the MINERVA trial
+ LINE-electronic PROs: ePRO-based intervention
used for symptom management in the Japanese
LIBRA trial — Possibility of treatment holds and dose
modifications/reductions to manage AEs
Other apps designed to monitor side effects of canoer therapies such as
ASyMS and MyChart
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
+ Different methods available for measuring adherence: eg, oral therapy checklists, pill counts, pharmacy and administrative
records, medical record review and clinician reports, self or caregiver reports, electronic medication monitoring systems
(MEMS), web-based or mobile applications (apps)
+ Patient education, counseling, and shared
decision-making (SDM) are essential
+ To improve adherence and persistence, educate
patients on:
— Features of their disease and risk status, potential
More electronic tools emerging to allow for remote
monitoring and tracking of AEs and adherence/persistence
)
D PROS captured using web-based or mobile apps
in abemaciclib clinical trials
o) TEANADD: us hato nació AES, implications o nonadherence
application reacting to patient self-reported — Prophylactic measures that can be taken to be
observations > used for AE monitoring and PROS | Better prepared to address potential AEs
(eg, providing patients with a prescription for
antidiarrheal medication and suggesting having that
always at hand should an episode of diarrhea occur)
in the MINERVA trial
+ LINE-electronic PROs: ePRO-based intervention
used for symptom management in the Japanese
LIBRA trial — Possibility of treatment holds and dose
modifications/reductions to manage AEs
Other apps designed to monitor side effects of canoer therapies such as
ASyMS and MyChart
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, PeerView
Key Takeaways
Important to implement team-based, patient-centric strategies and tools for prophylaxis, monitoring, and
management of AEs in patients undergoing treatment with CDK4/6 inhibitors and improving adherence and
persistence to allow patients to stay on therapy
- Dose modifications play an important part: start at the full dose, but have a low threshold for dose
reductions should patients experience AEs
Important to provide patient education and engage them in care decisions
= Inform patients of AE profiles of the CDK4/6 inhibitors, preventive and management measures, and
potential need for dose reductions, conveying that they don't decrease efficacy but can help with AEs,
enabling the important goal of staying on therapy to derive maximum benefit
There is a continuing need for improved and earlier management of AEs with concomitant
medications, patient education, and/or dose modifications to achieve a tolerable dose
and treatment adherence/persistence
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
Important to implement team-based, patient-centric strategies and tools for prophylaxis, monitoring, and
management of AEs in patients undergoing treatment with CDK4/6 inhibitors and improving adherence and
persistence to allow patients to stay on therapy
- Dose modifications play an important part: start at the full dose, but have a low threshold for dose
reductions should patients experience AEs
Important to provide patient education and engage them in care decisions
= Inform patients of AE profiles of the CDK4/6 inhibitors, preventive and management measures, and
potential need for dose reductions, conveying that they don't decrease efficacy but can help with AEs,
enabling the important goal of staying on therapy to derive maximum benefit
There is a continuing need for improved and earlier management of AEs with concomitant
medications, patient education, and/or dose modifications to achieve a tolerable dose
and treatment adherence/persistence
PeerView.com
PeerView.com/AGR827 Copyright © 2000-2024, Peerview
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