Nurses at the Forefront of Maximizing the Potential of TROP2-Targeted Therapy in TNBC and HR+, HER2- Breast Cancer: Best Practices for Adverse Event Management and Patient Education

Chair Jamie Carroll, APRN, CNP, MSN, discusses breast cancer in this NCPD/ILNA/AAPA activity titled “Nurses at the Forefront of Maximizing the Potential of TROP2-Targeted Therapy in TNBC and HR+, HER2- Breast Cancer: Best Practices for Adverse Event Management and Patient Education.” For the full presentation, downloadable Practice Aids, and complete NCPD/ILNA/AAPA information, and to apply for credit, please visit us at https://bit.ly/3SdnvWt. NCPD/ILNA/AAPA credit will be available until May 8, 2025.

1. Empower, Educate, Excel

Nurses at the Forefront of Maximizing
the Potential of TROP2-Targeted Therapy
in TNBC and HR+, HER2- Breast Cancer

Best Practices for Adverse Event Management and Patient Education

Jamie Carroll, APRN, CNP, MSN
Assistant Professor of Oncology | %
Nurse Practitioner MA 4
Mayo Clinic y
Rochester, Minnesota ®

Go online to access full NCPD/ILNA/AAPA information, including faculty disclosures.

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2. PeerView.com/USZ827

Our Goals for Today

Augment your knowledge of the structure, mechanism of
action, efficacy and safety profiles, and evolving roles of TROP2-
targeting ADCs in TNBC and HR+, HER2- MBC

Improve your ability to recognize, prevent, and manage AEs
associated with TROP2-targeting ADCs in TNBC and HR+,
HER2- MBC

Enhance your skills in implementing best practices for patient
education and provision of team-based, patient-centric, equitable
care to all patients with TNBC and HR+, HER2- MBC.

3. TROP2-Targeting ADCs in TNBC
and HR+, HER2- Breast Cancer:

Understanding the ADC Basics and Latest
Advances in the Treatment Landscape

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4. ADCs: Understanding Their Composition and Structure’

‘Antigen targetireceptor
High homogeneous expression in tumor
Limited/absent expression in normal tissue
Limited heterogeneity
Efficient intemalization following
ADC binding

Drugipayload
+ Highly potent (eg, microtubule inhibitor,
DNA-damaging agents)

Amenable to linker attachment

Maximized drug-to-antibody ratio

1. Marks S, Naidoo J. Lung Cancer 2022:163:50-68.

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‘Antibody
High affinity and avidity for target antigen

+ Long halflife

+ Conjugation sites with minimal impact on
‘ADC stability, internalization, and
pharmacokinetics (eg, cysteine, lysine)

+ Chimeric or humanized (decreasing
immunogenicity)

Linker
+ Controlled release of payload
= Noncleavable (eg, lysosomal
degradation of mAb)
= Cleavable (eg, acid/redox/iysosomal
sensitive)

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5. Introduction to ADCs: Targeting TROP2'

Sacituzumab Govitecan Datopotamab Deruxtecan
EE
ii aa
a crise
a? eae
N /G N ei
svat pm ae
re
; =
arr
/ EN
= EA
“omic hate’ | anti TROPZ 1961 mab ersemal govt Me nds] E
: zum
antitumor effect —_— | TROP2
EE
EE
1. Paris Cet al. Cancer Treat Rev. 2023:118:102572. PeerView.com

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6. Mechanism of Action of TROP2 ADCs’

Neighboring
Tumor tumor cells
microenvironment

— nn

Tumor cells that express TROP2 on Gore N
the surface undergo the cytotoxic ""

effects of the payload of the TROP2-

targeting ADC as a result of its

intracellular uptake, whereas the

adjacent cells can experience this
effect by its extracellular release

(bystander effect)

cells due tothe bystander effect

1. Pavone G eta. Molecules, 2021:267294 PeerView.com

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7. Current Role of TROP2-Targeting ADC Therapy
in Breast Cancer

+ Sacituzumab govitecan: first and currently only FDA-approved TROP2-targeting
ADCs in breast cancer
— Regulatory approval and indications of SG in metastatic TNBC and HR+,
HER2- advanced/metastatic breast cancer
+ NCCN guideline recommendations for sacituzumab govitecan:
— Category 1 preferred 2L regimen in metastatic TNBC
— Category 1 preferred 2L regimen for patients with recurrent unresectable or
metastatic HR+, HER2- breast cancer who are not candidates for
trastuzumab deruxtecan

+ Datopotamab deruxtecan not yet approved, but biologics license application
(BLA) accepted in the US for patients with previously treated metastatic HR+,
HER2- breast cancer

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8. ASCENT: Sacituzumab Govitecan (SG) in TNBC12

PFS Analysis SG (n = 235) Chemo (n = 233) OS Analysis SG (n = 235) Chemo (n = 233)
Events 167 150 Events 173 199
Median PFS, mo 56 17 Median OS, mo 124 67
HR = 0.39 (95% Cl, 0.31-0.49; P< .0001) HR = 0.48 (95% Cl, 0.39-0.59; P < .0001)
10 100
so
zo =
Ed g
£ « 8 «
grcturumab govtecan
» Seciturumab govtecan %
3 6 9 12 15 18 21 24 27 290 I o 3 6 9 2 15 8 21 24 27 30
Time, mo Time, mo

In 2020, the FDA granted regular approval to SG for treatment of unresectable locally advanced/metastatic TNBC
with 22 prior systemic therapies (21 for metastatic disease) based on results from the phase 3 ASCENT trial evaluating
SG vs a single-agent chemotherapy of the physician's choice

1. Bardia A ea. Eng J Med, 2021:304:1520:1541.2. Barca A etal ASCO 2023, Abstract 1071. PeerView.com

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9. TROPiCS-02: SG in HR+, HER2- MBC"

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Saumapewancann | À à Warren Magra) = 47310)
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So nw) mm me me HHL) vue mim Mm sm va WAM HAH am aa
me MO zu We Wen OU US EU Mm Men am MON TaN Ham) Oa)
1.Tolaney S et al. ASCO 2023, Abstract 1003, PeerView.com

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10. TROPiCS-02: SG in HR+, HER2- MBC"

In February 2023, the FDA approved sacituzumab govitecan for patients with
unresectable locally advanced or metastatic hormone-receptor HR+, HER2- (IHC 0,
IHC 1+, or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy

and at least two additional systemic therapies in the metastatic setting

TROP? testing is not required

1. Tolaney 5 et al. ASCO 2023, Abstract 1003. PeerView.com

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11. TROPiCS-02: Safety of SG in HR+, HER2- MBC"

TPC

sG

BEE) (n= 268) (n= 249)

Grade 23 TEAE 199 (74) 149 (60)

TEAES leading to treatment discontinuation 17 (6) 11(4)

TEAES leading to dose delay 178 (66) 109 (44)

TEAES leading to dose reductions 91 (34) 82 (33)

TE SAEs 74 (28) 48 (19)

TEAEs leading to death 6(2) 0
Treatment-related 4 (<1 o

The most common
grade 23 TEAES were , 3
neutropenia (52%), an a ca
darthea (10%) a si 8

and anemia (7%) 30) 16 10)
vn sa E
in the SG group, m 00) 4@)
and neutropenia (39%), oo EI 20)
thrombooytopenia (4%), s u .
wo Er so
fatigue (4%), and en 2000) so
dyspnea (4%) in the Hu aay 20
TPC group 1 m 20)
20 cn °

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1.Tolaney S et al, ASCO 2023, Abstract 1003,

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12. Primary Results From TROPION-Breast01:
PFS by BICR (Primary Endpoint)!

TROPION-Breast01: randomized, open-label phase 3 trial evaluating datopotamab deruxtecan (Dato-DXd) vs investigator's
choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine) in patients with inoperable or metastatic
HR-positive, HER2-low, or -negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have previously progressed on or are not

Suitable for endocrine therapy per investigator assessment and have received at least one systemic therapy

Dato-DXd icc

Median PFS, mo (95% Cl) 6.9 (5.7-7.4) 49(42-55)

.63 (95% Cl, 0.52-0.75; P< .0001)

PFS, Proportion

Dato-DXA (n = 365)
Ice (n= 367)

PFS by investigator assessment: median 6.9 vs 4.5 month: 0.64 (95% Cl, 0.5:

4. Bardia A et al. ESMO 2023, Abstract LEAN PeerView.com

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13. Primary Results From TROPION-Breast01:
Response Rate and Interim OS!

Response Rate

40 =Partial response = Complete response OS: Dual Primary Endpoint
x ‘ORR: 36.4
g 35 ene OS data were not mature: median
3 30 follow-up 9.7 mo
g 3 ORR: 22.9 Atrend favoring Dato-DXd was
£ 20 observed: HR = 0.84 (95% Cl,
E us 0.62-1.14)
2
51 The study is continuing to the next
2 5 planned analysis for OS
50% greater response rate with
Dato-DXd (n = 365) ICC (n = 367) Dato-DXd vs ICC

50% greater response rate with Dato-DXd vs ICC

1. Bardia A et al, ESMO 2023, Abstract ALBA. PeerView.com

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14. Primary Results From TROPION-Breast01:
TRAEs in 215% of Patients!

System Organ Class + Most TRAES were grade 1-2 and manageable
Pr Term, n (%
Blood and lymphatic system disorders * AESIs
‘Anemia 4041 Am 6420 7(2 — Oral mucositis/stomatitis: led to treatment
Neutropenia 39(11) 441) 14942) 108(31) discontinuation in one patient in the Dato-DXd
Eye disorder see
Dyes nl RE) 20 270) 6 — Ocular events: most were dry eye; one patient
discontinued treatment in the Dato-DXd group
Gastrointestinal disorders - Adjudicated drug-related ILD: rate was low;
Nausea 1845) 5(1) 8329 2(1) mainly grade 1/2
Stomatitis 180(50) 236) 46(13) 9(8)
Vomiting 7120) a) 27) 2)
Constipation 65 (18) 0 20) 0
Adjudicated Drug-Related ILD Dat icc
8524) ATA race n(%) te) ©
‘Skin and subcutaneous disorders
‘Alopecia 13136) 0 7221) 0
Grade 23, n (%) 20) o
Adjudicated drug-related ILD CITO) 0
1. Bardia A tal, ESMO 2023. Abstract #LBA11 PeerView.com

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15. Select Phase 3 Trials of TROP2 ADCs in Breast Cancer

Cc NCTO4639986 NCTO4595565 NCT05374512 NCT05382299 NCTO5382286
EVER132-002 SASCIA TROPION-Breast02 ASCENT-03 ASCENT-04
Stage Vv Localized w Vv v
‘Subtype HR+, HER2- HER2- TNBC TNBC TNBC
Sacituzumab govitecan
m A Datopotamab Sacituzumab govitecan + pembrolizumab vs
pode izumab govitecan deruxtecan vs vs chemotherapy Pembrolizumab +
Intervention (er DUR PA vs chemotherapy (paclitaxel, (paclitaxel, chemotherapy
ae (capecitabine, nabpaciitaxel, nabpaciitaxel, or (paclitaxel, nab-
pe a carboplatin, cisplatin) capecitabine, gemcitabine + paclitaxel, or
carboplatin, or eribulin) carbopl gemeitabine +

carboplatin)

+ Other ongoing trials with SG: ASCENT-05, ASCENT-07, ELEVANTE TNBC
+ Other ongoing trials with datopotamab deruxtecan (Dato-DXd): TROPION-Breast03

portant to

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16. Maximizing the Potential of TROP2-
Targeting ADCs in Breast Cancer:

Provision of Equitable Care, Adverse Event
Management, and Patient Education

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17. Recognizing Disparities and the Need to Provide Equitable
Care to All Patients With Breast Cancer

+ Disparities and inequities exist across the entire cancer care continuum, disproportionately affecting
medically underserved populations encountering cultural, linguistic, economic, and other barriers to care’?

+ Contributing factors: social determinants of health, access to care, variable quality of care, differences in
treatment, implicit bias, and many other patient- and system-level factors

Female Breast Cancer Incidence [777

and Death Rates by Race/Ethnicity, US*

10.

Some examples and facts:

+ Black women have lower rates of diagnosis of breast cancer than
White women, but are diagnosed at a younger age, at later stages,
with more aggressive forms like TNBC (=21%), and have the

highest death rate*

Racial and ethnic minorities are more likely to experience delays in
therapy, less likely to obtain adequate treatment, and significantly
underrepresented in clinical trials5$

4. Wong St. J Oncol Pract 2015:11:193-194. 2. HRSA: Medically Underserved Areas and Populations. Ntps:/bhw hrsa gov/shortage
3 Dean LT et al Cancer Causes Cont 201829:911:18. 4. Amarcan Cancer Soc Brest Cancer Facts and Figure 20192020 5 Foy KG at at NPY Brest in
Cancer 2018:47. 6. Duma N etal. J Oncol Pract. 2018:14:21-e10. PeerView.com

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18. Sacituzumab Govitecan: Outcomes by Race’

In the phase 3 ASCENT trial, 12% of patients self-reported their race as Black

Progression-Free Survival Overall Survival
BICR Anais so(n28) TRC (n= So (n=28) TRC (n=3
en Tacos Te wo Bas TE
ss 22 es
a Mase F55.no 6540) at (220 5 MesanOS,mo SEC) air) airs)
HRC 044(024080) P= 008 HR 85% 00) Omas
to zo
¢ g
Ë « 8 «
ie so
» Tec
o o
OTT TS eT OD MNMB UOT TES OTIS SCT REE TE TT UTM MaNES
Time, mo Time,
Per Per
SS "m A 91615 298 es 53333332210 S 28°28 26 29 25 2 221 Bisse 75545110
me Raise oa 2411111000000 m MS 31 2s 38 2 20 1 BHESS65422240
Safety in TT population reporting Black race
The most common treatment-related adverse events (TRAEs; SG vs TPC) of any grade in this subgroup were neutropenia (64% vs 61%), diarrhea
(64% vs 13%), and fatigue (52% vs 39%)
+ The most common TRAEs (SG vs TPC) of grade 3 in this subgroup were neutropenia (48% vs 42%), anemia (12% vs 6%), leukopenia (8% vs 16%),
‘and febrile neutropenia (8% vs 3%)
— The safety profile of SG in this subgroup was consistent with that of the full rial population
G should be considered for and discussed wi uding Black patients, with previously treated mTNBC
1. Carey eta SABCS 2021. Poster PS-1607 PeerView.com

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19. Overcoming Disparities in Breast Cancer
Clinical Trial Participation?”

Clinical trial participants should reflect the GAN
diversity of the general population, but

racial/ethnic minorities are underrepresented Black people living with MBC would consider
in clinical trials: Black people represent only participating in clinical trials
4%-6% of patients in all cancer clinical trials

BECOME Research Project aims to better ACTIONS >>>
represent Black people in cancer research by
increasing access to clinical trials for MBC:

2.
httos:/www.mbcalliance.ora/projects/become O) &S

Methods: web-based survey of US adults Better Inform Inspire Trust Ensure Access Address Concerns
living with MBC, following a literature review
and key informant interviews only
Results presented at ASCO 2022 mua) (ESL) 67% 64% 32%
want in dificuly believe treatment

Full report: https://www.mbcalliance.org/wp- will be fal

content/uploads/BECOME-Final-Report-FULL pdf same racial El
thnic identity

1. Wong SL. J Oncel Pract. 2018;11:193-194. 2. hitps:fbhw.hrsa.gowshortage-designaion/muap. 3. Dean LT et al. Cancer Causes Control 2018:26:511-618,
4: Ns /hw cancer orpicontenidamicancer-ogresearer/cancer.act-and staistca/reast-cancerfctr-andEgures breast cancer facts-and-fgures 2019-2020 pt E
5. Foy KC etal NPU Breast Cancer 201847. 6. Duma Net al J Oncol Pract 2018:14:e1-e10. 7. Waker S et al. ASCO 2022. Abstract 1014, PeerView.com

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20. Importance of Team-Based Collaboration and
Patient-Centered Care!

Sn Asian Rehabilitation
Gas

1. ps /acsjoumals oninelbrary wiley comidoU10.3322!caae 21249,

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21. Case 1: Treatment Selection for a Patient With HR+, HER2-
MBC With Disease Progression

A 68-year-old woman with a history of invasive carcinoma of the breast (no special type), pT2N2, grade 3, ER+
(90%), PgR+ (50%), HER2- (1+) received adjuvant chemotherapy > radiation > adjuvant Al for 4 years before
discontinuing because of side effects (joint pain)

5 months later, developed right hip pain > imaging revealed lytic bone lesions

Staging scans revealed liver metastases and bony metastases involving spine/hip/ribs

Biopsy of the liver: ER+, PgR+, HER2 0; BRCA1/2 negative

She began therapy with fulvestrant + CDK4/6i, and after a sustained response (26-mo PFS), she developed
asymptomatic progression in bone and 1.5-cm new liver lesions

ctDNA testing revealed an ESR1 mutation

She received elacestrant, followed later by exemestane and everolimus, then capecitabine

Disease has progressed, and further therapy is indicated

Liver biopsy and testing: disease still ER+; HER2 is IHC 0

The following treatment options were considered for and discussed with this patient: ADCs sacituzumab govitecan,
Dato-DXd, and T-DXd + other chemotherapy options + clinical trial participation

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22. How to Explain What ADCs Are to Patients
in Simple Terms?!

Key functions

Target antigen Recognition of target
cancer cells

Antibody Guidance system

for cytotoxic drugs

Linker Bridge between
antibody and drugs

and to control the release
of drugs inside cancer

cells

Warhead for
destroying cancer cells

Cytotoxic drug

1.FuZ.etal. Signal Transduct Target her. 2027.93 PeerView.com

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23. Case 2: Educating and Informing a Patient With mTNBC
Experiencing Disease Progression

A 54-year-old patient presents to your clinic after undergoing lumpectomy with radiotherapy for pT2NO,
invasive breast cancer, triple negative

Received AC-T chemotherapy
Noticed increase in shortness of breath, which prompted restaging scans that revealed pulmonary and

liver lesions; CT-guided biopsy revealed breast adenocarcinoma, ER-/PR-/HER2-; PD-L1 negative;
BRCAWT

Started carboplatin (AUC = 6)

Disease progression after 5 months

Treatment recommendation: sacituzumab govitecan
Let's discuss: How would you inform and educate this patient
about what to expect from treatment, including potential AEs?

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24. Educating Patients About AEs Associated With SG

Inform patients: in the clinical trials of SG, most common AEs (including laboratory abnorm:
+ Fatigue

Alopecia
Constipation
Increased glucose
Decreased albumin
Vomiting

+ Decreased leukocyte count
Decreased neutrophil count

Decreased hemoglobin

Diarrhea

Nausea

Decreased lymphocyte count

s) reported in 225% of patients included
Decreased appetite

Decreased creatinine clearance

Increased alkaline phosphatase

Decreased magnesium

Decreased potassium

Decreased sodium

jence any of the following side eff

+ Burning or pain
When they urinate

they experience diarrhea during
treatment wth sacituzumab govitecan
Black or bloody stools

‘Symptoms of dehydration, such

as lightheadedness, dizziness,

or faintness

Inability to take fuids by mouth

due to nausea or vomiting

Diarrhea that is not under control
‚within 24 hours

Hypersensitivity and
Infusion-Related Reactions

they experience the following

‘symptoms during their Infusion

‘or within 24 hours afterwar

+ Swelling of face, lips, tongue,
cr throat

+ Hives

+ Skin rash, hing, or fushing
of their skin

Fever

Difficulty breathing or wheezing

Hypotension

Chills or shaking chil (rigors)

Nausea
and Vomiting

Nausea or vomiting

that is not controlled

‘wth the medicines

Prescribed for them

+ Encourage your patients to communicate with you and other healthcare providers to proactively manage potential AEs
+ Develop an AE management plan to help support your patients

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25. Case 2: Patient With mTNBC Receiving SG
Develops Neutropel

A 54-year-old patient presents to your clinic after undergoing lumpectomy with radiotherapy for pT2NO,
invasive breast cancer, triple negative

Received AC-T chemotherapy

Noticed increase in shortness of breath, which prompted restaging scans that revealed pulmonary and
liver lesions; CT-guided biopsy revealed breast adenocarcinoma, ER-/PR-/HER2-; PD-L1 negative;
BRCA WT

Started carboplatin (AUC = 6)
Disease progression after 5 months
Treatment recommendation: sacituzumab govitecan

Let's discuss: How would you inform and educate this patient
about what to expect from treatment, including potential AEs?

On C2D1 noted to have ANC = 800; afebrile
Let's discuss: What should be done next?

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26. Management of Sacituzumab Govitecan-Induced

Neutropenia’

[ANC <1,500/mm on day 1 of any
Ioycie, ANC <1,000/mm? on day 8
lof any cycle, or neutropenic fever

Hold treatment until improved

Severe Neutropenia
Grade 4 neutropenia (ANC
<500/mm') lasting 27 days

* Grade 3 febrile neutropenia
(ANC <1,000/mm? and fever
238,5" C)

+ Grade 3/4 neutropenia which
has delayed dosing by 2-3
weeks for recovery to grade
st

use 24

1. Spring LM etal, Oncologist. 2021:26:827-734.

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Day 1 Onset
Daily 6-
4 and 5 or 4-6 (avoid

or after SG infusion)

Hold treatment until grade <1
‘Assess weekly for grade 3 and
biweekly for grade 4

I delay >3 weeks, discontinue
25% SG dose reduction

(7.5 mg/m?)

+ 50% SG dose reduction
(5 mg/m?)

|» Administer growth factors as

clinically indicated

Any Occurrence

Day 8 Onset
Pegylated G-CSF

(pegfilgrastim or
biosimilar) 24-48
hours post-infusion

-CSF on days
hours before

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27. SG Dose Modifications: Neutropenia

+ Important to discuss dose modifications with patients experiencing AEs!

Severe Neutropenia

Adverse Reactions

Grade 3-4 neutropenia that lasts 27 days,
OR
Grade 3 febrile neutropenia,

At time of scheduled treatment, grade 3-4
neutropenia which delays dosing by 2 or 3 weeks
for recovery to grade <1

At time of scheduled treatment, grade 3-4
neutropenia which delays dosing beyond 3 weeks
for recovery to grade <1

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Occurrence

First

Second

Third

First

Dose Modification

25% dose reduction from the original dose
and administer G-CSF

50% dose reduction from the original dose
and administer G-CSF

Discontinue treatment and administer G-CSF

Discontinue treatment and administer G-CSF

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28. Case 2: Patient With mTNBC Receiving SG
Develops Neutropel

54-year-old patient presents to your clinic after undergoing lumpectomy with radiotherapy for pT2NO,
invasive breast cancer, triple negative

Received AC-T chemotherapy

Noticed increase in shortness of breath, which prompted restaging scans that revealed pulmonary and
liver lesions; CT-guided biopsy revealed breast adenocarcinoma, ER-/PR-/HER2-; PD-L1 negative;
BRCA WT

Started carboplatin (AUC = 6)
Disease progression after 5 months
Treatment recommendation: sacituzumab govitecan
During the 2nd cycle develops neutropenia -> under control with management > treatment continues
During next cycle of treatment patient develops grade 2 diarrhea

Let's discuss: What should be done next?

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29. Management of Sacituzumab Govitecan-Induced Diarrhea’

‘Onset during or shortly after infusion

Delayed Onset
* Standard loperamide (4 mg + 2 mg

after each loose stool, up to 16 mg/day)
+ Dietary management

‘Severe Diarrhe:

+ Grade 23

+ Grade 1/2
progressing to
grade 3/4

Consider hospital admission
Begin intravenous fluids

Octreotide 100-150 mog SC TID
Consider antibiotic therapy as indicated

1. Spring LM et al, Oncologist. 2021;26:827-734

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+ Atropine 0.2 mg IV every 15 minutes for 2 doses, if required
+ Subsequent doses of atropine 0.2 mg IV for a total of 1 mg
+ Additional prophylaxis with atropine for future infusions

Discontinue loperamide
12 hours after last
diarthea episode
Dietary management

High-dose loperamide

(mg +2 mg
every 2 hours)

Ifnot resolved after 24 hours:

* Octreotide 100-150 mog
SC TID

+ Replace fluids/electrolytes

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30. SG Dose Modifications: Other AEs

Severe Non-Neutropenic Toxicity

Adverse Reactions Occurrence Dose Modification

Grade 4 nonhematologic toxicity of any duration,

25% dose reduction

FES from the original dose

Any grade 3-4 nausea, vomiting, or diarrhea due to treatment

that is not controlled with antiemetics and antidiarrheal agents, 50% dose reduction
OR Second

from the original dose

Other grade 3-4 nonhematologic toxicity persisting for >48 hours
despite optimal medical management,

OR

Grade 3-4 non-neutropenic hematologic or nonhematologic Third Discontinue treatment
toxicity at the time of a scheduled treatment that delays dosing

by 2 or 3 weeks to achieve recovery to grade <1

Grade 3-4 non-neutropenic hematologic or nonhematologic toxicity e A
which does not recover to grade <1 within 3 weeks

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31. SG: Management of Other TRAEs'

+ Pre-infusion medication for patients receiving sacituzumab govitecan is recommended

A + Observe patients closely for infusion-related reactions during each sacituzumab govitecan infusion and for

H MIES at least 30 minutes after completion of each infusion

+ Medication to treat such reactions, as well as emergency equipment, should be available for immediate
use

+ Premedicate with a two- or three-drug combination regimen (eg, dexamethasone with either a 5-HT;
receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention
of chemotherapy-induced nausea and vomiting (CINV)
INEM CIELO - withhold sacituzumab govitecan doses for grade 3 nausea or grade 3/4 vomiting at the time of scheduled
VO mi iti ing treatment administration and resume with additional supportive measures when resolved to grade $1

+ Additional antiemetics and other supportive measures may also be employed as clinically indicated; all
patients should be given take-home medications with clear instructions for prevention and treatment of
nausea and vomiting

1. tps aecessdata da goviérugsatida_docsMabel/2020/761 118500005 pt. PeerView.com

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32. Counseling Patients About Alopecia on SG

+ Hair loss is common with SG
+ Some tips that may help patients:

If you are considering a wig, buying it before treatment begins can help you
match it to the color and style of your hair

Check to see if your insurance company will cover the cost for a wig (cranial
prosthesis)

Wear a hair net at night or sleep on a satin pillowcase to keep hair from
coming out in clumps

Protect your scalp from the sun by using sunscreen, and wear a hat or scarf
outside

The effectiveness and safety of cooling caps is still being researched in clinical
trials, but it is an option that can be discussed and considered

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33. Case 3: Ocular Toxicity

Q A woman aged 73 years was diagnosed with screen-detected right invasive
ductal carcinoma: ER 21%-30%, PgR negative, HER2 2+, FISH ratio negative,
axillary lymph node positive

> Clinical stage: cT2 cN1
Q Germline genetics: negative
Q Medical history: anxiety and glaucoma
Q Surgical history: hysterectomy

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34. Case 3: Ocular Toxicity (Cont’d)

Q Consented to enrolling in a neoadjuvant clinical trial: randomized to Dato-DXd
Q Ophthalmology consult prior to treatment revealed increased pressure in eyes
from glaucoma; switched to latanoprostene bunod eye drops

Q End of February: started on study and received first dose of Dato-DXd

O Started eye drops: propylene glycol 1 gtt both eyes daily, pred forte 1 gtt both
eyes daily, netarsudil/latanoprost ophthalmic solution 1 gtt both eyes daily

Q C3: eye pruritus and increased secretions

Q Referred back to ophthalmology and dx with bilateral periocular inflammation

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35. Case 3 (Cont’d): Periocular Inflammation

Q Consented

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Dato-DXd

ire in eyes
d

1 gtt both
daily

mmatio

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36. Relevant Ocular Toxicity Grading Scale According
to Common Terminology Criteria for AEs (CTCAE)!

Ocular Toxicity

Blurred vision

Dry eye

Keratitis

Corneal ulcers

Decreased vision

Grade!

None

‘Asymptomatic,

with clinical observation only

‘Asymptomatic,
with clinical observation only

None

None

Grade Il

‘Symptomatic, moderate
decrease in visual acuity that
is 20/40 or better;

3 lines from baseline

‘Symptomatic, moderate
decrease in visual acuity that
is 20/40 or better;

3 lines from baseline

‘Symptomatic, moderate
decrease in visual acuity that
is 20/40 or better,

3 lines decreased vision from
baseline

None

Moderate decrease in visual
acuity that is 20/40 or better;
3 lines from baseline

Grade Ill

‘Symptomatic, marked
decrease in visual acuity that
is 20/40 to 20/200;

23 lines from baseline

‘Symptomatic, marked
decrease in visual acuity that
is 20/40 to 20/200;

23 lines from baseline

‘Symptomatic, marked
decrease in visual acuity that
is worse than 20/40, up to
20/200;
>3 lines of decreased vision

Ulcer but no perforation

Marked decrease in visual
acuity that is worse than
20/40, up to 20/200;

23 lines of decreased vision
from baseline

Grade IV

Visual acuity of 20/200
or worse

‘Symptomatic, marked
decrease in visual acuity that
is 20/200 or worse

Severe keratitis, with
perforation; visual acuity of
20/200 or worse

Ulceration and perforation

Marked decrease in visual
acuity that is 20/200 or worse

1. psp cancer gov/protocoldevelopment/electronie_appicaons/docs/CTCAE_v5_Quick Reterence_8.5x11,pd.

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37. Ocular Surface Events Management Guidelines!

Step 1: Prophylaxis

Advise patients to

+ Use artificial tears (four times daily for prevention and up to
eight times daily if clinically needed)

+ Avoid use of contact lenses.

Step 2: Confirm

Ophthalmologic assessment to ensure an accurate
diagnosis, event grading, appropriate treatment,
and event resolution should be considered

Comeal Toxicity Severity Grading Scale
‘Normal: Clear comea, no epithelia defects
Grade 1: nonconfluent superficial keratitis
Grade 2: nonconfluent superficial keratitis, a comea defect,
or 3-line or more loss in best corrected distance visual acuity
Grade 3: corneal ulcer or stromal opacity, or best corrected,
distance visual acuity <20/200
Grade 4: corneal perforation

Step 3: Manage

Ensure patient is adhering to prophylactic guidelines,
regardless of grade

Grade 1
+ Consider obtaining ophthalmologic assessment
+ No change in Dato-DXd dose

Grade 2

+ Obtain an ophthalmologic assessment

+ Delay dose until event has been resolved to grade <1,
‘and then maintain dose

Grade 3

+ Obtain an ophthalmologic assessment

+ Delay dose until event has been resolved to grade <1,
and then reduce dose by one level

Grade 4
+ Obtain ophthalmologic assessment
+ Discontinue Dato-DXd

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38. ILD/Pneumonitis

CTCAE

a Grade1 Grade Grade 4 Grade 5

Arma cnn E Sere symone, estenengresgnoy

Pneumonitis diagnostic observations only; intervention indicated; limiting self-care ADL;
Tionenionrcindesed img nal AGL "onygenndcatd—g,ineenten nated

"Potential questions to ask your patients to help with identification of ILD:
+ Have you been coughing recently? Is it a dry cough?
+ Have you had any shortness of breath, especially during or after physical activity?
+ Have you experienced any new breathing or respiratory problems?

+ If you already have respiratory problems, have they gotten worse?
+ Have you hada fever?

+ Have you been feeling tired?
+ Have you lost weight?

+A dsorder characterized by inflammation focally or iso) affecting he lung parenchyma PeerView.com

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39. ILD/Pneumonitis Management Guidelines!

Step 1: Monitor

Rule out ILD/pneumonits a patent develops
radiographic changes potentially consistent with
ILDIpneumonts or develops an acute onset of new or
‘worsening pulmonary or other related signs/symptoms,
Such as dyepnes, cough, or fever

Step 2: Confirm

+ Pulmonary function tests
+ Pulse oximetry (SP0;)

<Gseose consultation as cnica nated) > Arterial lod gases, Y cinicaly indicated
Bios culture and complete blood count, aná + One blood sample calecion for PK analysis
ther bood tests as needed as soon as ILDipneumonits is suspected,
- Bronchoscopy and bronchoalveolar lavage, ffeasble

cincaly indicated and feasible

{All LD/pneumonits events, regardiess of severity or seriousness, must be followed
‘until resolution, including after discontinuation of Dato-DX4

Example lung scan from a patient with adjudicated ILDIpneumonitis

tr four cycles of Dato-DXd

@

4. Heist RS et al. Cancer Treat Rev. 2024:425:102720.

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Step 3: Manage

Hold Dato-DXd for any ILDIpneumonitis events, regardless of grade

rade 4
Monitor symptoms and closely flow up in 2-7 days for onset of cinical symptoms and SpO;
Consider follow-up imaging in 1-2 weeks (or as cnica indicated)
Consider starting systemic steroids
Hold Dato-DXa unt fly resolved, then
~ifresolved in 528 days trom onset date, maintain dose
= if resolved in >28 days from onset date, reduce dose one level
= ifthe grade 1 ILDipneumenitis event does nat resolve

thin 84 days from ie last nfusion, permanently discontinue Ihe Dato-DXa

rade 2
+ Permanenty discontinue Dato-DXa
+ Monitor symptoms closely, and reimage as cicaly indicated
= Prompt stat treatment with systeme steroids
+ worsening or no improvement is observed in <5 days, then
= Considr increasing the dose o steroids
trative etiologies (vum to Step 2)

Hospitalization required
Prompt inate high-dose systemic steroids

- Reimage as cinicaly indicated

+ to improvement within 3-5 days, then
= Reconsider work-up for aternatveetologies (retun to Step 2)
~ Consider other Immunosuppressanis andlor teat pr local practice

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40. Detecting and Managing ADC-Related ILD:
The Five S Rules!

Gt

Screen

ez

C=

Scan

©

Suspend
Treatment

Steroids

+ Careful patent selection
is warranted before
initiating T-DXd to
‘optimize the monitoring
strategies based on
the baseline risk

+ Screening continues
‘during treatment,
with regular clinical
‘assessments to exclude
signs/symptoms of ILO

+ The fundamental

diagnostic tools for ILD
remain radiological
scans, with preference
for high-resolution CT
‘scans of the chest

+ Abaseline scan is

recommended, with
repeat scans to be
pertormed every 6-12
weeks

1. Tarantino P, Tolaney SM. JCO Oncol Pract. 2023:0P2300007,

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+ Minimizing the risk
‘of ILD involves.
‘teamwork, whieh
Includes educating

Patients and the entire
‘care team, as well

as mutidiscipinary
management once
ILD is suspected

+ T-DXd should always
be interrupted if LD is
‘suspected: can only
be restarted in the
‘case of asymptomatic
ILD that fuly resolves

+ The mainstay
for treating T-DXd-
induced ILD remains
corticosteroids, with
the dose to be adapted
to the toxic grade

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41. Oral Mucositis/Stomatitis Management Guidelines!

+ Oral mucositis/stomatitis has been Step 1: Prophylaxis Step 2: Confirm
observed in clinical trials of Dato-DXd Inte dy OCP pie administration Example image of stomatitis after one week
+ Mechanism is undetermined, but + Gent brushing teeth ater meal and a Decime sing à

TROP2 is known to be expressed on | siens unesshenmespanstecany

mucosal surfaces, including
epithelium of esophagus, tonsil
crypts, and salivary gland, suggesting
a possible on-target off-tumor
mechanism of toxicity

* In the Dato-DXd clinical trial program,

oral mucositis/stomatitis is an AESI ‘Optimize prophylaci and supportive medications for any orl
defined by selected preferred terms, |" ret ont ventions of ete
including stomatitis and mouth F «grade a 2 Dt dos recommendations

ulceration, of which stomatitis is the : + Grade 2: Comer a dove ely o reducn inte

most commonly reported; other Saat iia
selected preferred terms include Gta fed tn nda the weve as en restore Sorbas, pm maton,
mouth ulceration, pharyngeal — Wpropnyactesupprive meeaton have steady been optimize, ly
inflammation, and oropharyngeal pain |" Re 7.

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42. Conclusions & Key Takeaways

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