Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities

Chair and Presenter, Komal Jhaveri, MD, FACP, Prof. Giuseppe Curigliano, MD, PhD, Professor Stephen Johnston, MA, FRCP, PhD, and Joyce O'Shaughnessy, MD, discuss breast cancer in this CME/MOC/NCPD/CPE/AAPA/IPCE activity titled “Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/3F97VZE. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.

1. Changing the Scenery in ER+, HER2- MBC
With New Oral SERDs and Combinations
Foundations, Evidence, and Practicalities

—-

Komal Jhaveri, MD, FACP
Patricia and James Cayne Chair for Junior Facuity
‘Associate Attending

Breast Medicine Service and Early Drug
Development Service

‘Section Head, Endocrine Therapy Research Program

Clinical Director, Early Drug Development Service
‘Department of Medicine

‘Memorial Sloan Kettering Cancer Center/Evelyn H.
Lauder Breast and Imaging Center

New York, New York, USA

Prof. Gluseppe Curigliano, MD, PhD
Full Professor of Medical Oncology
Department of Oncology and
Hemato-Oncology

University of Milano

Director

Division of Early Drug Development

for Innovative Therapies

European Institute of Oncology, IRCCS
Milano, Italy

Professor Stephen Johnston, MA, FRCP, PhD
Professor of Breast Cancer Medicine & Head of
Medical Oncology

‘Consultant Medical Oncologist &

Head of The Breast Unit

‘The Royal Marsden NHS Foundation

Trust & The Institute of Cancer Research
Chelsea, London, United Kingdom,

Joyce O'Shaughnessy, MD
Celebrating Women Chair in Breast Cancer
Research

Baylor University Medical Center

Texas Oncology.

Sarah Cannon Research Institute

Dallas, Texas, USA

Go online to access full CME/MOC/NCPD/CPE/AAPA/IPCE information, including faculty disclosures.

Copyright © 2000-2025, PeerView

2. Fundamentals and Strategic Insights on
Oral SERDs in ER+, HER2- MBC

How to Overcome Endocrine Resistance

Komal Jhaveri, MD, FACP JP rrotessor Stephen Johnston, MA, PhD
Patricia and James Cayne Chair for Junior Faculty ; Professor of Breast Cancer Medicine &

r
ba

Head of Medical Oncology

Consultant Medical Oncologist &

Head of The Breast Unit

Section Head, Endocrine Therapy Research Program The Royal Marsden NHS Foundation
Clinical Director, Early Drug Development Service Trust & The Institute of Cancer Research
Department of Medicine Chelsea, London, United Kingdom
Memorial Sloan Kettering Cancer Center/Evelyn H

Lauder Breast and Imaging Center

New York, New York, USA

Associate Attending
Breast Medicine Service and Early Drug
Development Service

Copyright © 2000-2025, PeerView

3. METAvivor: A Resource for Pa

METAVIVOR

Metastatic Breast Cancer Research, Support and Awareness

nts, Care ers, and Provide:

METAvivor exists to sustain hope for those living with stage 4 metastatic breast
cancer (MBC) and is a volunteer-driven, nonprofit organization that funds vital
research to help improve the longevity and quality of life for patients with MBC

Research Advocacy Support
Makes every dollar count Rallies public attention to Helps patients find
as they work with the urgent needs of the strength through
researchers to extend MBC community support and purpose

and improve quality of
life for patients with MBC

www.METAvivor.org A PeerView

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4. Our Goals for Part 1

Enhance your knowledge of the limitations of standard
ET and the impact of ET resistance in ER+ breast cancer

Improve your understanding of the potential of novel
ER-targeting agents such as oral SERDs and combinations
to address unmet needs in ER+, HER2- MBC

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5. Understanding the Limitations of Standard ET
and Mechanisms of Endocrine Resistance in
ER+ Breast Cancer

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6. Questions & Considerations

+ What occurs in ER+ MBC after first-line therapy, and how does this impact
options and outcomes for patients?

Copyright © 2000-2025, PeerView

7. tations of Standard ETs and Implications fo

Al, tamoxifen, fulvestrant
+ Toxicity challenges

Thane
rene, ES
+ Nonadherence is an issue due to toxicity EEE; Loss ot ER
Pr see
Tamoxifen

+ Weaker ER suppression
Fulvestrant
+ Poor PK

+ Poor oral bioavailability necessitates IM administration
> limits dose and dose-dependent efficacy

+ IMinjections can be painful, burdensome, and require

in-office administration; patients often prefer oral options den] Creates Nes ane

+ Modest efficacy post-CDK4/6i | | | |
Activity limited in presence of ESR1 mutations ni | ac SER capac an
ro vanced A
1. WIM elal Nat Rev Cancer 2028:23.673-685, PeerView

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8. Genomic Landscape of En ine Resistance After Treatment

With Hormonal The

Frequency of Genomic Alterations Pattern and Frequency of Functional Mutations
(Treatment Naive vs Hormone Treatment) and Focal Amplifications or Deletions After ET

Frequency of Alteration

hr
SO . Sari

1. Raza Pet Cancer Col 2018:34 427-438. PeerView

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9. Selected Acquired Resistance Mechanisms to

Aromatase Inhibitors’

Hormonal

Mutations of the

EStrogen Receptor 1
gene (ESR1)

ESR1 encodes estrogen
receptor alpha, which is
an isoform of ER

+. Raza P ta. Cancer Cell 2018:34 427-4396, PeerView

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10. Number of Treatment Lines in ER+ BC!

Location of Somatic Point
Mutations in ESR1

Alterations in ER+ Tumors

*
a

#2 2

Hl =
He -
Eo

li >|

as ° 2

E Primary "Early MBC” Late MBC

Tumors

Mutation observed in primary ER negatve BC,
4. Jeseisohn el el Cin Cancer Res 2014:20:1757-1767.

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100 200 30 40 5
Frequency of Recurring ESR1 Genomic

Frequency, %

Frequencies of Genetic Alterations
in Primary vs Metastatic BC

m Primary
= Metastasis

05

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11. Activating ESR1 Mutations: Mechanism of Action

ESR1 Mutant + Primary tumors: not detectable
= + First relapse: rare (<5%)
+ Progression on Al: frequent

‘Adjuvant phase Metastatic phase
A ,
Diagnosis * Relapse Progression

ery + CT # RT 5.3%
| 6e A

= ESRI mutation
= ESRI wildtype

Potential therapeutic targets

E
1. seseohn Ret a. Caner Gel 2018:22:173-186 6,2. Alouchery Vet. Breast Cancer As. 2019200. PeerView

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12. Biomarkers in ER+, HER2- MBC:
To Test or Not to Test, What, and When

Copyright © 2000-20:

13. Questions & Considerations

+ The role of biomarker testing in ER+ breast cancer is rapidly evolving
- What to test?
- When to test?
- How to test—tissue versus liquid (cDNA)?

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14. The Evolving Role of Biomarker Testing in ER+, HER2- MBC"

Current guidelines recommend that treatment choices be informed by prior treatments and routine
testing for activating mutations in ESR1, PIK3CA, and AKT? and for inactivation of PTEN

ESR1 Mutations: Liquid Biopsy Testing Is the Standard'

IDNA testing identified more ESR1 mutations

than contemporaneous biopsy

‘Contemporaneous Paired Samples.

10) 10 10 889
912 10 579 967

AKTT -HER2 ESRI PIK3CA
n=39 n=3 n=39 n=39
PCR vs tissue sequencing binary status agreement
concordant negate Discordant tissue postive, ¿PCR negative
Ticoncordant postive [MDiscordant tissue negate, dPCR positive
1.Tumer NC etal. Lancet Oncol 2020;21:1296-1308,

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develop different

Metastatic

breast cancer
Blood APN

Nite oz DNA analysis __

won — EYE

WOO BHEBEHEE
PeerView

ar

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15. Questions & Considerations

+ Are there circumstances when biomarker testing before 1L therapy is
warranted in ER+ MBC?

+ Is there a rationale for biomarker-agnostic use of therapies in 1L and 2L
settings of ER+ MBC?

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16. Next-Gen Therapies at the Inflection Point:
Foundational Considerations and Strategic
Insights Into Targeting ER With Oral SERDs

and Combinations

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17. Questions & Considerations

jew classes of ER-targeting therapies showii
reast cancer, and how do they worl

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18. Numerous Novel Endocrine Agents Under Investigation’?

_——

Elacestrant
Imunestrant
Giredestrant
Amcenestrant
Camizestrant
Rintodestrant
D.0502
20716

LSZ102
SDC0B10

SDcos27.

AZ09496 e
Vepdegestrant (PROTAC)
OP-1250 (CERAN)

Fulvestrant Bazedoxitene

‘Oral SERDS

Raloxifene Tamoxifen
Lasofoxilene — Toremifene
H38.6646 (SERCA)|

Green: approved for distinct indications.
Blue: eurent in cinkal development
‘Orange: clinical development discontinued

1. MeDonnel OP etal. J Gin Onc. 2021.39:1383-1388, 2. Ferro E etal. Cancer Treat Rev. 2022:109:102432.

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19. Questions & Considerations

What are the different approaches and settings in which the new ER-targeting
therapies are being evaluated?

Where do you foresee the novel ER-targeting therapies having the greatest
impact and fitting within the treatment arsenal for ER+ MBC and EBC?

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20. Patient Perspectives and Experiences:
Insights From METAvivor

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21. Part 1 Summary and Conclusions

Copyright © 2000-202:

22. Novel Oral SERDs and
Combinations in ER+, HER2- MBC

Interpreting the Evidence and Implications for
Real-World Practice

Komal Jhaveri, MD, FACP Prof. Giuseppe Curigliano, MD, PhD
Patricia and James Cayne Chair for Junior Faculty Full Professor of Medical Oncology
Associate Attending Department of Oncology and

Breast Medicine Service and Early Drug Hemato-Oncology

Development Service University of Milano

Section Head, Endocrine Therapy Research Program Y Director

Clinical Director, Early Drug Development Service

Division of Early Drug Development
Department of Medicine for Innovative Therapies

Memorial Sloan Kettering Cancer Center/Evelyn H European Institute of Oncology, IRCCS
Lauder Breast and Imaging Center Milano, Italy

New York, New York, USA

1000-2025, PeerView

23. Our Goals for Part 2

Equip you with knowledge about the efficacy and safety
of oral SERDs, other novel ER-targeting therapies, and
rational combinations in ER+, HER2- MBC

Enhance your understanding of the clinical and practical
implications of the recent studies assessing new and
emerging ER-targeted therapies in ER+, HER2- MBC

Copyright © 2000-2025, PeerView

24. Innovations in ER-Targeting Therapy
for ER+, HER2- MBC
Oral SERDs, Combinations, and Beyond

Copyright © 2000-2025,

25. Overview of Select Oral SERD Trials in Pretreated

ER+, HER2- MBC

EMERALI SEREN AMEERA-34 ERA

Treatment Elacestrant Camizestrant? Amcenestrant Giredestrant
FulvestranvAls/
Control arm FulvestranvAls Fulvestrant ee Fulvestranv/Als
Phase (N) P3 (478) P2 (240) P2(867) P2 (303)
nie Men or postmenopausal Postmenopausal Men or women (any Men or women (any
women women menopausal status) | menopausal status)

ESRIm, % 48 34 464 39
Prior CDK4/6i (%) Required (100) Permitted (51) Permitted (80) Permitted (42)
Allowed prior fulvestrant Yes No Yes Yes
Allowed prior
chemotherapy in MBC. vor Yee vos ves
Data readout Positive Positive Negative Negative

4. Bidard FC etal. J Cin Oncol 2022.40:3246:3256.2. Olvera M et al Lancet Oncol 2024/25-1424-1439, 3 Its: astrazeneca comimeda.centre/press.teleases/
20ISIcamizesrant-mproved ps--hy-breastcancerii 4 Toaney SM eta, ESMO 2022, Abstract 212M0. 5 Tolney SMe al JChn Orca, 2023414014404. De e je
6. Marin Metal. ESMO 2022. Abstract 211MO. 7. Matin M etal. J Cin Oncol. 2024:42:2148-2160.

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26. I SERDs Over

acelERA BC AMEERA-3 EMERALD
2° EP: PFS (ESR1m) 2° EP: PFS (ESR1m) Co-1° EP: PFS (ESR1m)
100 100 100
A 9 9
La HR = 0.60 Éd HR = 0.90 2 HR =0.55
m mPFS:53v53.5mo , 70 mPFS: 3.7 vs 2 mo 7 mPFS: 3.8 vs 1.9 mo
seo & 60 (417) Seo (41.9)
ge 2 so go
2 40 2 40 2 40
Giredestrant
20 30 ia © Elacestrant
20 20 20
10 10 PCET 10
o o ot
0 2 4 6 8 10 12 14 0 2 4 6 8 10 12 14 16 18 20 0 2 4 6 8 10 12 14 16 18 20 22 24
Time, mo Time, mo Time, mo
Matin tal ESMO 202 Abel 210.2 Tor PeerView
A A ey SM ét al ESMO 2022. Art 212MO. 9. Did FC la J Cin Orel 2022.40 3246-2256.

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27. Questions & Considerations

Based on these trials, 40% across the board develop early progression
on monotherapy and 60% have <6 months benefit. Do we
need rational combination approaches to expand the benefits?

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28. EMBER-3: Baseline Demographic and Disease Characteristics‘

Imtunestrant
Imlunestrant SOC ET Imlunestrant
Characteristic x OC ET + Abemaciclib] Characteristic
(n= 334) (n= 830) * Abemaci
Median age, y (range) 61 (28-87) 6227-89) 62(3597) Visceral 57 54 38
Female. % 90 99 EJ Site ofmetastases,% Liver 22 30 2
Postmenopausal % 24 26 8 Bone only 22 25 2
Write E E 52 7 Primary 8 1 8
Race, % Asian 2 29 34 Endocnne resistance, %° secondary 92 ES 9
Black 3 2 4 TT Adjuvant 32 E 20
East Asia 25 26 El Msn En ABC 6 ES es
North America Overall 59 E 65
Region % — westemEuope 38 a e Previous CDKAIG,% Adjuvant 4 5 3
ther a ES 2 ABC ES ES 62
PRE 78 79 74 Palbocicib 61 08 65
ESRI mulation, 2 36 2 Pamesa Ribocicib 20 2 2
therapy, 2°

En ET rm Abemacicib 10 4 7

( Baseline characteristics were generally well balanced, including in patients with ESR1m

* Samples analyzed by Guardant360 COx, excep or patents from China where samples were analyzed by OncoCorpass Target assay” Includes single nuclecte variants and
Insertions/deletions of PIKICA, AKT, or PTEN analyzed by Guartant380 cIDNA assay, ths analysis excudes patents om China or wth unknown ESR Im status. Per ESO-ESMO
Intemational Consensus Guideines for ABC (ABC 6 and 7). Adluvant ET = fst Ine; ABC = second ine. © Percentages calculated based on the numbers of patents who received por.
‘COK@/S (mimestrant, n= 195; SOC ET. n= 189; munestant + abemaccib.n = 130) PeerView
{shaved KLet al SABCS 2024, Presentation GS1-01. 2. Jhaver KL et al. N Eng. Med, 2025,392:1189-1202.

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29. = Median PFS
Imlunestrant 5.5 mo
a5 SOC ET 3.8mo
x HR; P 0.62; < 001
w 50
a 25%
25 Imlunestrant

0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
No. at Risk Tame; moi
Imlunestrant 138 95 74 56 45 35 22 18 15 8 4 4 3 E o 0
soc 118 74 51 33 19 7 5 3 2 1 0 o 0 0 0 0

Imlunestrant led to a 38% reduction in the risk of progression or death in patients with ESR1m

“The median fofow-up was 16.7 months in the ilunestrant am and 13.8 months in the SOC ET am.
Due to evidence of nonproportonal hazards, a senstty analysis of PFS using RMST was conducted. Estimated RMST at 19.4 maths was 7.9 months

(959% Ci, 68.8.1) nthe munestant arm vs 5.4 months (95% Cl, 4.62) i the SOC ET am (dfferenoe 26 months (12-39). PeerView
1. «raven KL et al SABCS 2024, Presentation GS1-01.2. Jhave KL et al M Engl J Med, 2025:392 1189-1202

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30. Imlunestrant SOC ET
(n=331) (n=330)

5 Events, n 237 253
¥ 30 Median, mo (95% Cl) 5.6 (5.3-7.3) 5.5 (4.65.6)
É HR (95% Cl) 0.87 (0.72-1.04)

a Imlunestrant P 12

+
o SOG ET Prespecified critical HR <0.84°
D246 8 04 1 de 2 ze da 2 2 30
Time, mo

No, at Risk
Imnestrant 391 225 173 135 118 89 62 47 43 30 20 19 13 10 0 0
SOCET 330 221 165 122 89 63 St 41 38 23 17 14 10 2 0 0

The majority subgroup of patients without ESR1m showed no difference in PFS. |
HR = 1.00 (95% Cl, 0.79-1.27)

The mdionfolon-up was 16.6 months in the munestrant am and 16.8 months inthe SOC ET em. > At fu alpha PeerView
4. «raven KL et al SABCS 2024, Presentation GS1-01. 2. Jhaven KL etal M Engl J Med, 2025:392.1189-1202

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31. EMBER-3 Primary Endpoint: Imlunestrant + Abemaciclib Improved

Investigator-Assessed PFS vs Imlunestrant Alone in All Patients’

Imlunestrant

E Imlunestrant
+ Abemaciclib

75 H (n= 213) (n = 213)"
x ! IR: ira Events, n 114 149
gs ! tg Median, mo 94 5.5
a ' (95% Cl) (7.5-11.9) (3.8-5.6)
2 H HR (95% Cl) 0.57 (0.44-0.73)
H P < .001
al H Imlunestrant
0 2 4 6 8 10 12 14 16 18 20 22 24 2% 28 30
No at Risk
IS 6 5 3 0 0 0
Imnestant 213 140 106 77 67 48 29 20 1 10 3 2 0 0 0 0
Imlunestrant + abemaciclib led to a 43% reduction in the risk
of progression or death over imlunestrant alone in all patients
(+ Ecacy analyses confined to the imunestant population concurrent rancomized to maestant + abemacki treatment arm The median folow-up vas.
aie Let al SASCS 2004 Psenatan 101,2. maven KL tat ME Hed 2025 082 1169-1202 PeerView

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32. EMBER-3 Subgroup Analysis

Imlunest

+ Abemaciclib

Provided Consistent Benefit Regardless of ESR1m Status

Patients With ESR1m

Imiunestrant

Imtunestrant
+Abemacieup lunes
nen m
100 EN 36 m
Mecian, mo a ss
ach aan 0872
7 HR (65% CN) 0.53 (0.35-0.80)
=
go Imlunestrant +
a abemaciclib

o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Time, mo
mans

penas ou 47 59 5 2 1 7 6 3 1 1 oo 8
mann x aw saw ee Ts eo ee os

Patients Without ESR1m*

100 7
Megan, mo 91 55
(98% ch (74144 0658)
75 HR (95% Cy 0.59 (043-081
e
Mi) Imlunestrant +
E abemaciclib

o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Time, mo
men ue sth Mo OM we 8 4 8 0 0 0
AO

Consistent benefit with imlunestrant + abemaciclib regardless of ESR1m status

* Patients wihout ESRIm Includes 6 wh unknown ESA fm slats (mlunestant + abemacil, n= 1:imunestrant, n = 7)
1. Shaver KL et al. SABCS 2024, Presentation GS 1-01. 2. Jhaver KL ll Engl J Med, 025,392 1189-1202

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33. EMBER-3 Subgroup Analysi

mlunestrant + Abemaciclib Provided Consisten!

r CDK4/6i and With PI3K Pathway Mutations’?

Patients With Prior CDK4/6i Treatment

Imlunestrant

purent miunestrant

(n= 140)

100 ay]
Everton 7 1
Megan mo 94 37
75 (95% Cl) (7211.2) (21-55)
4 HR 5% ©) 051 (0380.45
gs Imlunestrant +
o abemaciclib

Imlunestrant

o
0 2 4 6 3101214 16 18 20 22 24 26 28 20
Time, mo
sos
mow ne
A O

Patients With PI3K Pathway Mutations?

Imiunestrant

mlunestrant imtunestrant

100 (n=88) CE]
Events,n E 70
Median, mo 78 38

bi (65% Ch (66-110) (6155)
HR (95% Cy 0.61 (0.42-0.87)

Imlunestrant +
abemaciclib

o
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Time, mo
ne sn
en @ nn mm ons 8 2 tt 0 0 0
MR 6 8 wo ow 6 7 8 4 2 0 0 0 0 0

Consistent benefit with imlunestrant + abemaciclib across key clinical subgroups

* Includes single nucleotide variants and insertonsidetetons of PACA. AKT1, or PTEN analyzed by Guardant360 DNA assay.
4. Shaver KL etal. SABCS 2024, Presentation GS1-01. 2. Jhaver KL ll M Engl J Med, 2025,392 1189-1202.

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34. EMBER-3: Investigator-Assessed PFS by Subgroup in Patients Previously

Treated With CDK4/6i—Consistent Benefit of Imlunestrant + Abemaciclib*?

Imlunestrant
+ Abemaciclib

Imlunestrant
Subgroup HR (95% CI) Interaction P

Events Total, ni

Patients previously treated

with COK4/6i 79139 109/140 oH 0.51 (0.38-0.68)
Abemacidib 910 1043 0.93 (0.37-2.31)
Prior CDK4/6i type
epee Palbocicib 4480 6086 0.43 (029-063) 180
Rbocicib 257 2289 0.57 (0.34-0.98)
Detected 28/53 5972 ei 0.44 (0.28-0.70)
ESRI mutation status 635
Notdetected 51/86 5068 m 0.55 (0.37-0.82)
PI3K pathway mutation Detected 3761 55163 Fe 0.52 (0.34-0.79) ve
aus Notdetected 4175 51169 ho 0.47 (0.31-0.72)
Detected 1329 3339 H=— 0.32 (0.16-0.63)

Concurrent ESR1 mutation

and PISK pathway mutation Status Not detected ate

65/107 73193 0.53 (0.38-0.74)

0% 05 1 2

Favors imlunestrant + abemaciclid Favors imlunestrant

«Ea ans confined tothe imanestant papa conan domi to mnestont + abemackib vestment rm A
‘tharos Relat SABCS 204 Preseraion 101 Saler ides. PeerView

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35. EMBER-3 Subgroup Analysis: Imlunestrant + Abemaciclib Showed Consistent

PFS Benefits in 1L and 2L Settings of Endocrine-Resistant ER+, HER2- MBC"

Patients With ESR1m All Patients
100 ao ei 100 00 Brera
Eu mer = =
ES 15 rana vaa oran
ris az y? ER Baer
Pr A gs
gs de inaescon» E stant
= an pr menace
soc A pre soc
° ob © re 02 4 E voiDi41610202224062030 EME TETE
Time, mo Time, mo Time, mo
100 as 100 100
5 — a. 15 in mo won ONAL $5975: 75 ia mon cn 0102111) 390759,
® mon sain ent À en Diner: "a E Ss aan
“Ee Er ES —
» ina 5 Imnestant« © 25 ‘bomen
Ñ Imunestani emscan soc
o

0.2.4 6 8 10121416162022242628303234
Time, mo

02 4 6 8 101218 161820222475 2830
Time, mo

0 2 4 6 8 1012181618202224262830324
Time, mo

Imlunestrant, as monotherapy or in combination with abemaciclib, provides an all-oral targeted therapy
option in the 1L or 2L setting for patients with endocrine-resistant ER+, HER2- MBC

EMcacy analyses confined to patients who were concurenty randomized.

1.Neven Petal. ESMO Breast 2025,

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36. EMBER-3: Safety Profile Was Generally Favorable’

Imtunestrant
TEAEs in 210% nna Imlunestrant + Abemacial
Era eee) TEAES net Imlunestrant+ Abemacicllb
Any Grade Grade 23 ere (n=208)

Patients win 21 TEAE » mo] e Any Grade Grade23

Fatigue 23 a 13 TE =

Danes 2 a 12 o en

Nausea 17 a ES o Neuropeniat 48

Aura 14 1 14 <« ane ss

AST increased 1 4 13 1 Fatigue 39

Back pain “1 1 7 a ies = 3

a ukopeniar

ALTincreased 10 4 10 1 er a

Anemia” 10 2 ” 3 ‘Abdominal pain" 20

Constipation 10 o 6 a Decreased appette 20
a Pa 7
Dose reductions due lo AE, % 2 o Dose reductions duelo AE, %! 39

iinvatons due lo AE 4 1

Deaths due lo AE on study. 2 A/A

Injection ste” 273208)

* Consolidated tern. ® N Ihe number of evaluable patents who received fuvestant.<N is the number of evaluable patents who completed the PRO-CTCAE survey
{answered yes” of" lo ijecton-site pain, swing, or redness) * Dose reducton of imlunestrant alone = 2%; ebemacia alone = 23%: both drugs = 14%, PeerView
Y <haves Ket al SABCS 2024. Presentation GS1-01. 2. Jhaven KL etal N Engi Med, 2025-392.1189-1202.

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37. + GHS/QOL and functional domains were maintained across treatment arms

- Notably, GHS/QOL and functioning were maintained with imlunestrant + abemaciclib
despite increased patient-reported diarrhea and nausea/vomiting

+ Both longitudinal and time-to-deterioration analyses of GHS/QOL numerically favored
imlunestrant vs SOC ET in patients with ESR 1m (5.6 vs 3.8 months; HR = 0.76 [95% Cl,
0.51-1.13]), suggesting that imlunestrant delays deterioration of QOL without meaningful
increases in toxicity

+ Importance of ISR as a clinically relevant AE for patients is demonstrated by the high
incidence (72%) of patient-reported ISR with fulvestrant

Consistent with the primary results from EMBER-3, these PRO results reinforce the
benefit of imlunestrant, as monotherapy or combined with abemaciclib, as an all-oral
targeted therapy option after progression on ET for patients with ER+, HER2- MBC

+. Gurñglano Get al. ASCO 2025, Abstract 1001. PeerView

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38. Questions & Considerations

What are the implications of EMBER-3?
Might the oral SERD + CDK4/6 inhibitor combination become the new standard in
the 2L setting?

Might the treatments tested in EMBER-3 have a role in the 1L setting for some
patients with ER+, HER2- MBC?

2000-2025, PeerView

39. SERENA-6: Switch ET Partner of CDK4/6i Therapy From Al

to Camizestrant When ESR1mut Is Detected in ctDNA12

SERENA-6: Phase 3, Randomized, Double-Blind Study

Step 1: ESR1m Detection Phase Step 2: Double-Blind, Randomized Treatment Phase

1L standard of care treatment with Al (letrozole or anastrozole) + CDK4/6i

Study treatment

Screening (N = 3,000) > | ESR Wi Second screening à
Key Inclusion Criteria Every 2-3 Treatment Cycles

+ Histologically confirmed + Centrally tested plasma ctDNA for
HR+HER2- ABC ESRI status

+ Received 26 months of 1L Al
(letrozole or anastrozole) +
CDK4/6i (palbocidlib, abemaciclib, progression by investigator
or nbocilb) therapy for ABC with assessment
no evidence of disease progression _ . Tumorimaging perstandardot "ECOG PSof Oor1

+ ECOG PS of0 or 1 ee - Adequate organ and marow

Key Inclusion Criteria Switch to camizestrant
+ ESRim detected by central testing 75 mg OD
of DNA
+ Evaluable disease
+ No evidence of disease

2 No rior exposure o camizestrant. ua prugrmssien function
fulvestrant, or an investigatonal ET
(in any seting)
PeerView
1. Tamer NO etl. ASCO 2025, Abstract LBAA, 2. Bide FC. Engl Med, 2025°93 560590.

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40. SERENA-6: Baseline Characteristics’?

Characteristic ey Su
Median age (range). y 61 29-81) 60.5 (35-80)
Female, n (2) 457 (100) 155 (98)
White 97 (62) 102 (65)
Rees cy) Asian/other 39 (2521 (13) 34 (221/22 (14)
Postmenopausal status, n (3%) 123 (78) 127 (80)
ECOG PS, n (9%) on 107 (68y48 (31) 98 (62756 (35)
Visceral metastases, n (99 66 (42) 71 (45)
84 (53)

At first test 84 (64)

Time of ESR1m detection, n (%)P Alas nites
Time from initiation of Al + COK4/6i ne BEN AN
to randomization, n (96)? Sd 60 (38) 58 67)
: Median (range) mo 23 (7-96) 23 (6-96)
un a Palbociclib 119(76) 119(75)
een Ribociclib 25 (15) 23 (15)
2 Abemacicib 14(9) 16 (10)
05386 70 (45) 82 (62)
Most common ESRIM
at baseline, n (%)* er se Ed

* Dala was missing fortwo patents ne camizesirant + COKAV6i am and tree patents in the Al + COK AI. One patent

the Al + CDKAV6i group had a score of 2,

‘which was a protocl devaion Sralfcabion factors. « Subsequent tests were performed every 2-3 mo after the iil test. Three most prevalent ESR Im detected of

the 11 quafyrng mutations, Patents may have had more then one ESRIM.
1. Tumer NC et al ASCO 2025, Abstract LBAd, 2. Bidard FC. Engl) Med. 2025:393:509-580,

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41. SERENA-6: Switching Al to Camizestrant & Continuing CDK4/6i,

Guided by ESR1m Emergence, Significantly Improved PFS'
Primary Endpoint: Investigator-Assessed PFS

Camizestrant + CDK4/6i Al + CDK4/6i

in = 157) in = 158)
PFS events, n 71 100
100 Median PFS (95% Cl), mo 16 (12.7-18.2) 9.2 (7.2-9.5)
90 Adjusted HR (85% Cl); P 0.44 (0.31-0.60); < 00001

80
„m 60.7 Camizestrant +
> 60 . CDK4/6i
g 50 | Alscokası
© 40 5
30 T
20 H
10 H
o Y +
0 3 6 9 12 15 18 21 24 27 30 33
. Time From Randomization, mo
No. at Risk
Camizestrant + CDK4/6i 157 138 105 82 55 41 2% AN 9 7 6 o
Al + CDK4/6i 158 124 73 55 29 17 7 3 1 o o 0
‘crosses ie estat fer signieane (P= 0001), PFS vas dened per RECIST 1.1. HRwasestmated using the Cox progotonal hazard model
jste for seiten feces PeerView

1. Tumer NC etal ASCO 2025. Abstract LBA4. 2. Bidard FC. N Engi Med. 2025:395:569-590,

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42. SERENA-6: Camizestrant + CDK4/6i Delayed Time to Deterioratio

4/6i'2
Time to Deterioration in Global Health Status/Quality of Life: EORTC QLQ-C30
Camizestrant + Al+
CDK4/6i (n = 107) CDK4/6i (n = 95)
400 Events, n 36 49
so Median TTD (95% Cl), mo 23(13.8-NC) 64(28-140)
Adjusted HR (95% Cl); nominal P 0:53 (0.33-0.82); <.001

Camizestrant +
CDK4/6i

Al + CDK4/Gi

Deterioration-Free
Survival, %

0 3 6 9 12 15 18 = 24 27 30 33
Time From Randomization, mo

No. at Risk
Camizestrant + CDK4/6i 107 72 59 0 24 16 9 6 3 2 2 o
Al + CDK4/6i 95 4 2% 6 1 8 2 2 À 1 1 o

Camizestrant + CDK4/6i also delayed the time to deterioration in pain compared with Al + CDK4/6i ]
PeerView

1.Tumer NC e al ASCO 2025, Abstract LBA, 2. Bidard FC. N Engl Med, 2025;383:569-580,

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43. SERENA-6: Camizestrant + CDK4/6i Was Well Tolerated!2

AEs (210% of Patients)

Camizestrant + CDK4/6i (n = 155) Al + CDK4/6i (n= 155)
Total/Grade 23 MGrade 1 MGrade 2 M Gradez3 MGrade 3 MGrade2 M Grade1 Grade 23/Total

Any AE, 145 (94%) Any AE, 135 (87%)
Neutroperia i TT 34/45
Anemia 17/5 CI 5/17
Leukopenia _
Photopsia 207 Tos 0/8 Nonhematological AEs
Arthralgia 1 Sn 1/17
Fatigue 150 DEEE i 1/14
Dee 120 DE m 07 osure time-adjusted incide:
Nausea 10/0 a EM 1/14 rates were similar bei
Back pain 10/1 EEE ER 0/10 treatment arms for neutr
Diarrhea So m m 1/11
Headache Sn m 0/13
TO 6 5 4 0% © m 00 10 2 % 4 0 6 7

Patients, %

Photopsia (brief flashes of light in the peripheral vision) did not impact daily activities: if experienced, visual effects had
no/minimal impact on daily activities, were typically <1 min, <3 d/wk, and reversible.
There were no structural changes in the eye and no changes in visual acuity.
Neutropenia is reported as a group term that includes neutropenia and decreased neutrophil count: anemia is reported as a group term that includes anemia and hemogiobin decrease:
‘euopensa reported a group tem tat incudes leutopona and vide loss cet count ezense. Bratycarda and snus Bratycard were rept in fe carzestant + COKE am
Sy. nei patents (52%) and four patents (2 63) respect. No (sas era ia AEs were grade 2, and none ofthese events equted treatment dszontnunten Impact of vu

‘hes was measured ing the Visual Symptom Assessment Gvesiomare lA
Fumer NG etal ASCO 2025 Asset LEMA 2 Bard FG Engl ed 20259956050 PeerView

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44. Questions & Considerations

What are the implications of SERENA-6?
How feasible and worthwhi this type of intensive ctDNA moi the real world

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45. Other Selected Clinical Trials of Combinati

and Targeted Agents in ER+, HER2- MBC

ADELA (NCT06382948)' pionERA (NCT060657 48)? evERA (NCT05306340)°

Elacestrant 345 mg PO QD Giredestrant 30 mg PO QD Giredestrant 30 mg PO QD

+ everolimus 7.5 PO QD + CDK4/6i PO QD/BID + everolimus 10 mg PO QD

| Ms lier gous NCTOS3#2048.2 Htpslricelis got NCTOEDESTAE, 3a goal NOTOSSOESA, PeerView

PeerView.com/XYR827 Copyrigh

46. Selection of 1L Oral SERD Trials in ER+, HER2- MBC

persevERA (NCT04546009)' SERENA-4 (NCT04711252)?

Giredestrant 30 mg QD
Palbociclib 125 mg
Letrozole-matched

placebo

Camizestrant 75 mg QD
Palbociclib 125mg
Anastrozole-matched
placebo

+ ER+, HER2-
LA/ABC

+ No prior systemic
tx for ABC

+ ER+, HER2-
LA/ABC

+ No prior systemic

tx for ABC

Anastrozole 1 mg
Palbociclib 125
Camizestrant-matched
placebo

N=978

Letrozole 2.5 mg N= 1,342
Palbociclib 125 mg
Giredestrant-matched

placebo

Primary endpoint: PFS Primary endpoint: PFS

1. Mes/iicaria gis INCTOASAG009. 2 ips rich os NCTOS741252. PeerView

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47. Selected Adjuvant Trials of Oral SERDs in ER+, HER2- EBC

a
after classification and completion
—
en
TREATGONA’ 3 ERF.HERZ- Olea ou d pesada camo PUM coa Alza ONES NCTOSS1236¢
en em
ee
(ypN+) and ctDNA detected:
7
mean RE, ci - ias
A A
O os
Ber
Bars
mn à onen "SORTASE opine: coneatety Coon setae, os normes
hiso aid letrazole) + abemackib
ann Sage idee, Opentabet GEST Sy: Tamoxten
ERAS 3 ER+,HER2- pe tr ” Substudy: giredestrant + Anastrozole IDFS NCTO4961996
heart RGT sy abemacicib 2y + Exemestane
chemo + Letrezote
en
. == =
cena à eue QUE, ne un Seg eet
LÉ
1. hitps://clinicattrials.gow'study/NCTOSS 12364. 2, https:lidinicalrials.gow'study/NCT05774951. 3. https/Iclinicaltrials gowstudy/NCTO5952557. P Vi
4. https:/iclinicaltrials. gowistudy/NCTO4961996. 5. hitps:/dlinicalrials. govistudy/NCTOS514054. eerview

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48. Questions & Considerations

What are your perspectives on the different strategies bei
ER+, HER2- breast cancer?

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49. Other Emerging ER: eting Agents!

Novel SERMs ER CERCA PROTAC CERAN
Selective estrogen

Selective estrogen Proteolysis. Complete estrogen
5 receptor covalent
receptor modulators ere chime otor antagonist
Lasofoxifene | H38-6545 | | Vepdegestrant | | Palazestrant |
Bazedoxifene (ARV-471) (OP-1250)

Novel ER-DRIVEN agents with different potencies of degradation vs antagonistic
activity and in different stages of development and disease contexts

= Antagonistic activity
(SERM)

Degradation
activity (SERD)

41, Hemando © etal. ASCO 2023 Educational Session. 2. Adapted from Cor C et al. Cancer Treat Rev. 2023:117:102568. PeerView
3. Hips hnwwplzer comnens/pressreuse/press-elease-celalarinas-and-plzer-announce-posiive-oplne-esuts-phase.

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50. VERITAC-2: Study Design’

: Global Phase 3 Trial of Vepdegestrant
28-Day Treatment Cycles

Key Eligibility Criteria
+ Agez18y
+ ER+, HER2- advanced or metastatic
breast cancer
+ Prior therapy
— 1 line of CDK4/6i + ET

Vepdegestrant (|
200 mg orally (onc

Stratification

— 51 additional ET ee ie

— Most recent ET for 26 mo see

— No prior SERD (eg, fulvestrant, en
elacestrant)

— No prior chemotherapy for advanced
or metastatic disease

+ Radiological progression during or after

the last line of therapy

Primary endpoint: PFS in BICR in the ESR1m population and all patients
+ Secondary endpoints: OS (key secondary), CBR and ORR by BICR, and AEs

Data cutof date: January 31, 2025.
* ESRIm status was assessed in CIONA by Foundation Medicine, except in China, where Origmes testing ws used. PeerView
Hamon E el al. ASCO 2025. Abstract LBA1000.2. Campone Metal N Engl J Med, 2025,383:556-560,

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51. VERITAC-2 Prim

BICR in Patients

Vepdegestrant Fulvestrant
100 (n = 136) 34)
90 Median follow-up, mo 74
80 6-mo PFS Events, n (%) 79 (58) 95 (71)
(95% Cl), % Median PFS, mo (95% CI) 5(3.7-74) 2.1 (1.9-3.5)
70 463 Stratified HR (95% Cl) 0.57 (0.42-0.77)
= 60 fe 2-sided P <.001
@ 50 (36.1:53.9)
ra
à 40
30
= Vepdegestrant
10 Fulvestrant
01234567 8 9 1011 12 13 14 15 16 17 18
Time, mo
No. at Risk
Vepdegestrant 136 134 87 78 55 53 38 37 22 22 15 14 10 8 4 3 3 2 0
Fulvestrant 13412562 52 30 29 15 12 8 8 7 2 1 1 1 1 0 0 0
PeerView

1, Hamiton E el al. ASCO 2025. Abstract LBA1000. 2. Campone Metal N Engl Med, 2025.393:558-568.

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52. VERITAC-2 Primary Endpoint: No Significant PFS Improvement

With Vepdegestrant by BICR in All Patients’?

Vepdegestrant Fulvestrant

100 Median follow-up, mo E
90 Events, n (%) 186 (59) 198(64)
80 Median PFS, mo (95% CI) 3.7 (36-53) 3.6 (2.2.3.8)
70 Stratified HR (95% CI) 0.83 (0.68-1.02)
X 60 2-sided P 07
g so
a 40
30
20 Vepdegestrant
10 Fulvestrant
ot
0 123456 7 8 9 1011 12 13 14 15 16 17 18
Time, mo
No. at Risk
Vepdegestrant 313 306 189 168 113 108 74 72 46 46 28 24 15 12 6 4 4 2 0
Fubestrant 311292162143 101 98 58 54 36 36 23 12 7 7 4 3 2 0 0
PeerView
4. Hamon Eel, ASCO 2025, Absta LBA1000.2. Campone Met Eng Med 2025303556560.

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53. VERITAC-2: Vepdegestrant Improved Investigator-Assessed PFS

in Patients With ESR1 Mutations’

Patients With ERS1m All Patients
Vepdegestrant Fulvestrant Vepdegestrant Fulvestrant
as ins 134 ons att
Events, n (%) 88 (65) 113 (84) Events, n (%) 211 (67) 224 (72)
100 Median PFS, mo (95% CI) 5.4(3.7-6.4) 2.8 (2.0-3.5) 400 Median PFS, mo (95% CI) 3.9(3.7-5.4) 3.6 (2.8-5.0)
‘Stratified HR (95% Cl) 0.52 (0.39-0.70) ‘Stratified HR (95% Cl) 0.83 (0.69-1.1)
so P <.001 2 P 06
80 6-mo PFS 80
70 70
go zo
gs ¢ 50
a 40 Ls
30 Vepdegestrant 30
E 3 Vepdegestrant
Le 0 Fulvestrant
o o
OTD SAS OTS 2118 15101718 O12 94567 SOOT 1916151017 18
Time, mo Time, mo
No. at isk No. at isk
186130 90 81 61 62 30 38 25 25 16 15 11 8 5 a 4 1 0 Vepsogestot 313904200177 189109 80 76 51 51 29 25 17 15 7 5 5 1 0
Da tuts 2 60 AAA 1 0 0 à Fe IE IN MN a db 2 18 9 8 32108
a
1.Hamon Et ASCO 2025, Attac LBAYOG0.2.Campone Metal N Eng Med 2025203556508. PeerView

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54. VERITAC-2: Vepdegestrant Is Well Tolerated!?

VERITAC-2: Safety and Tolerability (All Treated Patients)

Overview TEAEs in >10% of Patients in Either Group
TEAES, % Vepdegestrant Fulvestrant Vepdegestrant Fulvestrant
(n {n = 307) % (n= 312) (n = 307)
Any grade 81
Grade 23 18
9 Fatique 27 1 16 1
Leading to treatment 3 7 AlTincreased 14 1 10 1
discontinuation AST increased 14 1 10 3
Reading lo. deso) 2 NA Nausea 13 o 9 1
reduction is
TRAES, % Anemia 12 2 8 3
Any grade 57 40 Neutropenia 12 2 5 1
Grade 23 8 3 Back pain 1 1 7 <1
QT Prolongation Arthralgia 1 1 11 o
+ TEAEs: vepdegestrant, 10%; fulvestrant, 1% Decreased
+ AQT interval sub-study (n = 88) confirmed a mild appetite 1 <1 5 0
increase (11.1 ms) from baseline in mean Qc:
with upper 90% Cl (13.7 ms) <20 ms, indicating no
large QT-prolonging effect
4 Hanon Ela. ASCO 2025 Ant LEA100.2.Canpone Mel EG He, 22599 556-588 PeerView

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55. Patient Perspectives and Experiences
Insights From METAvivor

Copyright

56. Part 2 Summary and Conclusions

Copyright © 2000-202:

57. Integrating Oral SERDs and Combinations
Into the ER+, HER2- MBC Treatment Arsenal

Practical Guidance for Multifactorial Clinical
Decisions

Komal Jhaveri, MD, FACP « Joyce O'Shaughnessy, MD
Patricia and James Cayne Chair for Junior Faculty # Celebrating Women Chair in Breast
Associate Attending Cancer Research

Breast Medicine Service and Early Drug Baylor University Medical Center
Development Service Texas Oncology

Section Head, Endocrine Therapy Research Program ‘Sarah Cannon Research Institute
Clinical Director, Early Drug Development Service Dallas, Texas, USA

Department of Medicine

Memorial Sloan Kettering Cancer Center/Evelyn H

Lauder Breast and Imaging Center

New York, New York, USA

Copyright © 2000-2025, Peerview

58. Our Goals for Part 3

Equip you with skills in developing individualized
treatment plans for patients with ER+, HER2- MBC
incorporating oral SERDs and combinations

Provide you with strategies for engaging patients in
shared decisions about treatment selection as well as
improving AE management and adherence when using
oral therapies

Copyright © 2000-2025, PeerView

59. Putting Data to Practice Step by Step
Considerations and Practical Strategies for Integration of
Oral SERDs, Combinations, and Other Therapies Into
Treatment Plans for Patients With ER+, HER2- MBC

60. Novel ER-Targeting Therapies and Combinations Changing the

Scenery in ER+, HER2- MBC'$

Rapid treatment advances have occurred with oral SERDs and other new ER-targeting therapies and
combinations for ER+, HER2- MBC:

+ Oral SERD monotherapy trials: Consistent benefit was demonstrated in patients with ESR1 mutations, but 40%
across the board still develop early progression on monotherapy and 60% still have <6 months benefit

+ EMBER-3: In patients with ER+, HER2- advanced breast cancer, imlunestrant led to significantly longer PFS vs
standard ET therapy among those with ESR1 mutations but not in the overall population, while imlunestrant +
abemaciolib significantly improved PFS vs imlunestrant, regardless of ESR1 mutation status or presencellack of
other alterations

+ SERENA-6: In patients with ER+, HER2- MBC with ESR1 mutations that emerged during treatment, those who were
switched to camizestrant with continuation of a CDK4/6 inhibitor during 1L therapy had significantly longer PFS vs
those who maintained the Al + CDK4/6i combination

+ VERITAC-2: In patients with ER+, HER2- MBC, vepdegestrant, a PROTAC, was associated with significantly longer
PFS vs fulvestrant in the subgroup with ESRT mutations but not in the full patient population

Where might these new therapies fit within the existing treatment algorithm?

1. Martin M et al. ESMO 2022. Abstract 211MO. 2. Tolaney SM et al. ESMO 2022. Abstract 212MO. 3. Bidard FC et al. J Cin Oncol. 2022:40:3246-3256. P: Vi
ve Hal NE td 2005392 188-1202 5 da FCN Eid Med 2005 25500-5608 Carpe el N Eng he 2025599 396 SE. eerView

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61. Let’s Start With a Case

A 59-year-old postmenopausal woman with ER+, HER2- MBC progressing
on 1L therapy

+ Diagnosed with de novo metastatic disease with numerous liver and bone
metastases involving spine, hip, and ribs. Received 1L CDK4/6i (ribociclib) + Al,
but after 18 months developed asymptomatic progression in bone and new liver
lesions
ctDNA testing revealed presence of ESR1 mutations but no PIK3CA/AKT/PTEN
alterations

+ No germline BRCA1/2 mutations

PeerVi

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62. Exploring Options Based on Recent Advances:

Potential Treatment Algorithm for ER+, HER2- MBC"

Adjuvant ET

Genomics

PIK3CA/AKT.

PIK3CA/AKT.

1L Treatment

Genomics

Fulv + CDK4/G
Imlun + abema

Fuly + CDK4/8i
Imlun + abema

Imlunestrant

1. Adapled from: Burstein H. SABCS 2024. Abstract GS1-02,

PeerView.com/XYR827

PIKBCHAKT.

PIK3CA/AKT.

2L Treatment

Imun + abema
Fuv + abema
Fulv + everol
Ímiun + abema

Elacestrant
Imlunestrant
Vepdegestrant
+æp
Fulv+ alpel

jane abana
Fulv + abema
mn + abema
Elacestrant
Imlunestrant
Vepdegestrant

3L+ Treatment

Other ET
Revisit priors
Chemo/ADC

Imlun + abema
Fuly + PISKVAKTI

PeerView

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63. Questions & Considerations

Which disease-, tumor-, treatment-, and patient-related factors and characteristics
should we consider in clinical decision-making and selection among 2L monotherapy
and combinatorial options?

What if no targetable alterations were found with biomarker testing?

What if the patient's tumor had a PIK3CA/AKT/PTEN alteration?

What if multiple alterations were detected?

Does the use of a specific CDK4/6i in the 1L setting matter in 2L treatment selection?

PeerView.com/XYR827 Copyright © 2000

64. Let’s Consider Another Case

A 62-year-old postmenopausal woman with ER+, HER2- MBC recurring after
adjuvant therapy
Had received prior adjuvant ET, but developed recurrence within 12 months of
completion of adjuvant Al therapy; currently has extensive visceral metastases
ctDNA testing revealed neither ESR1 nor PIK3CA/AKT/PTEN alterations
No germline BRCA1/2 mutations

Copyright © 2000-2025, PeerView

65. Exploring Options Based on Recent Advances:
Potential Treatment Algorithm for ER+, HER2- MBC’
Adjuvant ET Genomics 1L Treatment Genomics 2L Treatment 3L+ Treatment
TENTE
Fe mel Other ET
Imlun + abema RCD
Elacestrant Chemo/ADC

Imlunestrant

PIKSOA/AKT GONAGuded
wich to

camzestant+
COR?) PIKSCA/AKT

lun +abemar

Fulv + abema

Fulv + COK4/6i —
Imlun + abema
Elacestrant

Fulv + CDK4/8i
Imlunestrant

Imlun + abema
Vepdegestrant

Imlunestrant

PIK3CA/AKT. PIK3CA/AKT.
PeerView

Copyright © 2000-2025, Peerview

1. Adapled from: Burstein H. SABCS 2024. Abstract GS1-02,

PeerView.com/XYR827

66. Questions & Considerations

+ Which disease-, tumor-, treatment-, and patient-related factors and characteristics
should we consider in clinical decision-making and selection among available and
emerging options?

Would an EMBER-3 regimen be appropriate as an all-oral option in the 1L setting for
the patient with endocrine-resistant disease (considering the findings and implications
of subgroup analysis by line of therapy from EMBER-3)?

What if the patient's tumor had an ESR1 mutation? What if a PIK3CA/AKT/PTEN
alteration were present? What if multiple concurrent alterations were detected?

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67. Improving AE Management, Adherence, and
Persistence With Oral Therapies

Copyright © 2000-2025, PeerView

68. Questions & Considerations

What do we know about patient burdens and preferences related to oral vs other routes of
delivery of breast cancer therapies in ER+, HER2- MBC?

Copyright © 2000-2025, PeerView

69. tient Perspectives and Prefe:

+ Availability of various modes of administration for breast cancer treatments brings into focus
the importance of patient preference

+ Patients are generally unwilling to accept reduced efficacy or greater treatment toxicity in
favor of other treatment attributes

fe © Accumulating evidence suggests that oncology patients prefer oral treatments to IM/I'
relevant factors/reasons include:

1. Cox AC, Fallows LJ. Eur y Oncol Nurs. 2007:11:43-48, 2. Eek Det al, Patient Prefer Adherence. 2016:10:1809-1621,
nexperience-melastal atrentoptons.

Y
Y

Y
Y

Y
ne

Convenience
Ability to receive
treatment at home
Needle anxiety
Avoidance of pain
Access

Reduced burden

3. Hips feractve Ameca group compat

PeerView.com/XYR827

jobreasteancertre

Y” Sense of greater control

v Feeling that they are actively
fighting their cancer

Y” Perceptions of efficacy and safety

v Past treatment experiences

v Stage and line of therapy

Y” Demographic characteristics

PeerView

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70. Questions & Considerations

+ How do the oral SERDs compare in terms of their AE profiles, and are there
considerations for management of specific AEs when using these therapies alone or in
combinations?

+ What guidance can you offer based on your experiences to maximize adherence and
persistence with the oral therapies?

Copyright © 2000-2025, Peerview

71. Graphical Representation of AE Profiles of Oral SERDs!

Elacestrant Camizestrant 75 mg Camizestrant 150 mg
E an, nes (890)
coun 62982 eave 19%) cough 948" ange warn) cough 6408 ae (19.10%)
UTRI (0%), o ‘Vomiting (19%) UTRI (6.67%) 20 Vomting (0%) UTRI 11%), Vomiting (0%)
‘Anemia 2 Decreased appette Anema 2 Decreased appette Anema = ‘Decreased appette
oo : Cao Goer) = Ea som à Gar
Bradycardia “ ‚Arthralgia rd, a Arthralgia. Bradycardia 10 Arthealgia
(0%) (14.3%). (0%) (4.05%) (16.44%) (12.33%)
Photopsia Dirmen Photopsia, Diarthea Photopsia. Diarmea
om (13.9%) zu (5.41%) (24.66%) (548%)
Fe EE A) a
. et
ATieceaed nern ALT nest potes AN nnd Asco
> ke
A uo. emo} Omen) ee A var ne SEB ay
stant) Constan 12) nan cama Corn Hs) AA E
Giredestrant Imlunestrant Amcenestrant
Ras, RE een
‘Cough (0%) 35° “aligue (7.33%) Cough (13%) 35 “atigue (28%) Cough (0%) 35 “atigue (11.2%)
UTRI (0%) E ‘Vomiting (8.66%) UTRI (10%) El Vomiting (0%) UTRI (0%), 30 Vorniting (19.6%)
Anemia = Decreased appetite Anemia: 25 Decreased appette Anemia er Decreased appetite
(239%) = (633%). >) 2 oo os > am
Bradycarda. 10. Atthraigia Bradycandia Arthralgie Bradycardia 10 Arthralgia
6) a ioe, R fe
Photopsia Dirhes Photopsia VE Dianthes Photopsin 2 Diarrhea.
rs osm) m IX en OTH) ch
FR mine Aena A san
‘Germ ee O m Kar re
ALT increased increased ALT increased AST increased ALT increased PT pa
(11335) Cl ¿0% ¿ore e Headend (1265)
Dyspepsia (0%) Headache (7.33%) Dyspepsia (0%) ‘Headache (1( Dyspepsia (0%)
‘Hot flush (0%) Constipation (6%) ‘Hot flush (10%) Constipation (0%) ‘Hot flush (9.1%) a
a
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72. Maximizing the Benefits of Oral Therapies: Factors Influencing

Adherence/Persistence and Interventions for Improvement!*

Adherence is a multidimensional phenomenon A variety of measures can be used
fluenced by various factors to improve adherence
Patient Related O Healthcare System o Therapy-Related Interventions. @
+ Perception of necessity, Related + Simplification of regimens
benefit, QOL + Shorter duration of + Education on the use of medications
+ Forgetting and self-efficacy: follow-up visits + Clear instructions
+ Preference for alternative + Prescribing errors + Patient-tailored prescriptions
+ Routinization + Different physicians + Continuous monitoring and reassessment of treatment
+ Depression or anxiety responsible for follow-up + Assessment and management of AEs
I + Relationship with HCPs
en Related a + Lack of patient involvement Patient-Related Interventions ®
2 Modifications and complexity .... ” decision-making + Interventions to redress treatment misconceptions
rn and encourage patient-oncologist dialogue
© Duration and variations Social and Economic + Assessment of psychological needs |
hero Related + Use of conventional (brochures) and digital
+ Younger or older age (web-based) tools to educate on the use of medications
- + Higher out-of-pocket cost + Remote monitoring tools for AEs and adherence
Disease Related O + Lower income and + Behavioral motivational intervention
+ Comorbidities education level + Good patient-provider relationship.
+ Unknown tumor size + Unmarried + Self-management of disease, treatment, and AEs
+ Node-positive disease
[Rosato 2 Vege et Cara Tes Rey 273361062 Fan ll Ba Coens To! 20787487 8 PeerView

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73. Patient Perspectives and Experiences
Insights From METAvivor

Copyright

74. Part 3 Summary and Conclusions

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