Practical Protocols for Preventing and Managing Antibody-Drug Conjugate-Associated Nausea and Vomiting

Karin Jordan, MD, PhD, discusses ADC-associated nausea and vomiting in this CE activity titled "Practical Protocols for Preventing and Managing Antibody-Drug Conjugate-Associated Nausea and Vomiting." For the full presentation, please visit us at www.peervoice.com/NFQ870.

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Practical Protocols for Preventing and Managing Antibody-Drug
Conjugate-Associated Nausea and Vomiting

Learning Objectives
Recall the emetogenic risk of approved antibody-drug conjugates (ADCs)

Explain why it is imperative for ADC-associated nausea and vomiting to be
optimally controlled from the beginning

Outline the guidelines for control of emesis for anticancer treatments that have a
moderate-high/high emetogenic risk

Propose appropriate protocols to prevent and manage ADC-associated nausea
and vomiting

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Part 1 of 4: Which ADCs Are Associated With a Moderate-High/High Risk
of Nausea and Vomiting?

Karin Jordan, MD, PhD

Head of Hematology, Oncology and Palliative Care
Ernst von Bergmann Hospital Potsdam

Potsdam, Germany

Professor of Medicine

University of Heidelberg

Heidelberg, Germany

Copyright © 2010-2024, P

3. PeerVoice

Karin Jordan, MD, PhD, has a financial interest/relationship or affiliation in
the form of:

Consultant for AstraZeneca and Daiichi Sankyo Company, Limited.
Advisory Board for Helsinn Healthcare SA.

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ADC Toxicities: Not a Class Effect

Cancer Type

Breast

Approved ADC
Trastuzumab emtansine

Characteristic Toxicity

Thrombocytopenia; elevated LFTs

PAM Breast; gastric; lung Trastuzumab deruxtecan ILD; nausea; neutropenia
E
5 Breast; urothelial Sacituzumab govitecan Neutropenia; diarrhoea; nausea
EI Cervical Tisotumab vedotin Ocular toxicity
3
ES ovarian Mirvetuximab soravtansine Ocular toxicity
Urothelial Enfortumab vedotin Neutropoenia; anaemia; rash
ALL Inotuzumab ozogamicin Haematological toxicities; hepatotoxicity
Be
ey AML Gemtuzumab ozogamicin Haematological toxicities; hepatotoxicity
Be
ah
FRE] cH; MF; sALCL; PTOL Brentuximab vedotin Haematological toxicities; PN
53 EA
I] DL8CL; HGBL Loncastuximab tesirine ama pie:
gamma-glumtamyitranseincrease
DLBCL Polatuzumab vedotin

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Emetogenic Potential of ADCs

Emetic Risk of ADCs (%, Frequency of Emesis)
NCCN Guidelines

High (>90%) Moderate (>30-90%)

+ Sacituzumab govitecan " 5 : + Brentuximab vedotin + Loncastuximab terisine
+ Trastuzumab deruxtecan Msc + Enfortumab vedotin + _ Tisotumab vedotin
+ Gemtuzumab + Trastuzumab emtansine
ozogamicin

* Inotuzumab ozogamicin

MASCC/ESMO Guidelines
Mode:

igh

+ Sacituzumab govitecan Brentuximab vedotin Loncastuximab terisine

+ Polatuzumab vedotin

+ Trastuzumab deruxtecan * Enfortumab vedotin + Mirvetuximab
+ Gemtuzumab soravtansine
ozogamicin + Tisotumab vedotin

+ _Inotuzumabozogamicin + _Trastuzumab emtansine

Bold text: ADCs with different classification risk between the two guidelines.

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Abbreviations and References

ADC Toxicities: Not a Class Effect

Abbreviation(s): ADC: antibody-drug conjugate; ALL: acute lymphoblastic leukaemia; AML: acute myeloid leukaemia;
CHL: classical Hodkin lymphoma; DLBCL: diffuse large B-cell lymphoma; HGBL: high-grade B-cell lymphoma;

ILD: interstitial lung disease; LFT: liver function tests; MF: mycosis fungoides; PN: peripheral neuropathy;

PTCL: peripheral T-cell lymphoma; sALCL: systemic anaplastic large cell lymphoma.
Reference(s): Hamilton EP. The ABCs of ADCs: What Does the Future Hold? American Society of
Annual Meeting (ASCO 2024); Oral Presentation.

ical Oncology 2024

Emetogenic Potential of ADCs

Abbreviation(s): ESMO: European Society for Medical Oncology; MASCC: Multinational Association of Supportive Care
in Cancer; NCCN: National Comprehensive Cancer Network.

Reference(s): Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Antiemesis; Version 1.2024.

Jordan K et al. Support Care Cancer. 2023;32:53.

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Part 2 of 4: Why Is It Imperative to Have an Antiemetic Protocol
for Patients Who Are Going to Receive ADC Therapies?

Karin Jordan, MD, PhD

Head of Hematology, Oncology and Palliative Care
Ernst von Bergmann Hospital Potsdam

Potsdam, Germany

Professor of Medicine

University of Heidelberg

Heidelberg, Germany

Copyright © 2010-2024, P

8. PeerVoice

Karin Jordan, MD, PhD, has a financial interest/relationship or affiliation in
the form of:

Consultant for AstraZeneca and Daiichi Sankyo Company, Limited.
Advisory Board for Helsinn Healthcare SA.

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Defining Nausea and Vomiting Based on Timing of Symptoms

Acute Nausea/Vomiting

Delayed Nausea/Vomiting

Long-Delayed Nausea/Vomiting

(2120 hrs)

+ Occurs within the first 24 hours
after treatment

+ Mainly triggered by the release
of serotonin from
enterochromaffin cells of the
small intestine

> Occurs from 24 hours to 5 days
after treatment

+ Mainly triggered by the
transmitter substance P, which
is found primarily in the area
postrema located outside the
BBB

+ Anewly recognised category of CINV
+ Affects a similar proportion of

patients and severity is similar

+ Patients experiencing N/V on days 4

and 5 are at a significant risk of
‘experiencing long-delayed N/V

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Anticipatory Nausea/Vomiting

+ “Learned” symptoms resulting
from a classical conditioning
process resulting from the
negative experience of N/V
during a previous course of
cancer therapy

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Patterns of Emesis

— Cisplatin
--- Other

Intensity of Emesis

Least
lo) 24 48 72 96 120

Time, hours

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sea and Vomiting Matters

Improves
comfort and
patient QoL

Prevents

Improves f r
psychological even
well-being À 7 Minimising malnutrition

Nausea and
Vomiting
Enhances
treatment
adherence

Reduces
hospitalisation

Contributes
to optimal
tumour
control

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miting Associated With Risk of Cachexia

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Nausea and

Risk of

„sel EEE) cancer

cachexia

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Abbreviations and References

Defining Nausea and Vomiting Based on Timing of Symptoms

Abbreviation(s): BBB: blood brain barrier; CINV: chemotherapy-induced nausea and vomiting: N/V: nausea and
vomiting.

Reference(s): Jahn F et al. Dtsch Arztebl int. 2022;119:382-392.

Chow et al. Support Care Cancer. 2023:31505.

Patterns of Emesis

Reference(s): Rapoport BL. Front Pharmacol. 2017;8:19. doi: 10.3389/fphar.2017.00019.
Chow et al. Support Care Cancer. 2023;31:505.
Karin Jordan, MD, PhD. PeerVoice interview; August 2024.

Why Early Management of Nausea and Vomiting Matters

Abbreviation(s): QoL: quality of life.
Reference(s): Bianchini G et al. Cancers (Basel). 2022:14:1022.
Karin Jordan, MD, PhD. PeerVoice interview; August 2024.

Nausea and Vomiting Associated With Risk of Cachexia
Reference(s): Jahn F et al. Dtsch Arztebl Int. 2022;19:382-392.

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Part 3 of 4: Precis of NCCN and MASCC/ESMO Guidelines, SmPCs, and Clinical Trial
Recommendations for the Management of ADC-Associated Nausea and Vomiting

Karin Jordan, MD, PhD

Head of Hematology, Oncology and Palliative Care
Ernst von Bergmann Hospital Potsdam

Potsdam, Germany

Professor of Medicine

University of Heidelberg

Heidelberg, Germany

Copyright © 2010-2024, PeerVoi

15. PeerVoice

Karin Jordan, MD, PhD, has a financial interest/relationship or affiliation in
the form of:

Consultant for AstraZeneca and Daiichi Sankyo Company, Limited.
Advisory Board for Helsinn Healthcare SA.

www.peervoice.com/NFQ870 Copyright © 2010-2024, PeerVoice

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MASCC/ESMO G

elines: Emesis Prevention Wit!

Emetic Risk Group

Minimal

ADC

Antiemetics

> EN

No routine prophylaxis

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NCCN Guidelines: Emesis Prevention With ADC Therapy

Option B

E

3 E | Days2,34 D

El I Bayi | Days234
M 1. Olanzapine 1. Olanzapine Olanzapine Olanzapine

E 2. NK-1RA 2. Aprepitant® Palonosetron

[a] 3. 5-HT3 RA 3. Dexamethasone Dexamethasone

DZ 4. Dexamethasone Option C

1. Aprepitant®

1. NK-1RA
2. Dexamethasone

2. 5-HT3 RA
3. Dexamethasone

All options are category 1 and

if aprepitant PO is used on day 1.
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5-HT3 RA for Nausea and Vomiting: What Are the Options?

“First Generation” Mode of
5-HT3 RA Administration + Similar efficacy and safety profiles

= Might be associated with an
Ondansetron Oral; IV increased risk for developing
Granisetron Oral: IV; SC (ER) abnormal electrical activity of the

heart that is detectable on ECG*

Dolasetron Oral

Most effective 5-HT3 RA in
controlling delayed nausea and
vomiting

31V dolasetron or 32 mg of ondansetron is no longer recommended for the prevention of nausea and/or vomiting,
because they have been associated with an increased risk for cardiac arrhythmias.

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NK-1RA for Nausea and Vomiting: What Are the Options?

NK-1RA Mode of Administration
Aprepitant Oral; Injectable emulsion
Fosaprepitant IV version of aprepitant
Netupitant? Oral
Fosnetupitant? IV
Rolapitant Oral
No major differences between NI

*Netupitant/fosnetupitant is only available in combination with palonosetron as part of the fixed-dose combination
agent NEPA (oral or IV, respectively).

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Abbreviations and References

MASCC/ESMO Guidelines: Emesis Prevention With ADC Therapy

Abbreviation(s): 5-HT3: serotonin; ADC: antibody-drug conjugate; DOPA: dopamine; ESMO: European Society for
Medical Oncology; MASCC: Multinational Association of Supportive Care in Cancer; MIRV: mirvetuximab soravtansine;
NCCN: National Comprehensive Cancer Network; NK-I: neurokinin 1; OLZ: olanzapine; Pola: polatuzumab vedotin;

RA: receptor antagonist; SG: sacituzumab govitecan; T-DXd: trastuzumab deruxtecan.

Reference(s): Herrstedt J; participants of the MASCC/ESMO Consensus Conference 2022. ESMO Open. 2024;9:102195.
doi: 10.1016 /jesmoop.2023.102195.

NCCN Guidelines: Emesis Prevention With ADC Therapy

Abbreviation(s): NCCN: National Comprehensive Cancer Network; PO: per os (by mouth).
Reference(s): Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Antieme:

Version 1.2024.

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Abbreviations and References (Cont'd)

5-HT3 RA for Nausea and Vomiting: What Are the Options?

Abbreviation(s): ECG: electrocardiogram; ER: extended release.

Reference(s): Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Antiemesis; Version 1.2024.
Herrstedt J; participants of the MASCC/ESMO Consensus Conference 2022. ESMO Open. 2024;9:102195.
doi: 10.1016/jesmoop.2023.102195.

NK-1 RA for Nausea and Vomiting: What Are the Options?

Abbreviation(s): NEPA: netupitant/palonosetron.
Reference(s): Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Antiemesis; Version 1.2024.
Herrstedt J; participants of the MASCC/ESMO Consensus Conference 2022. ESMO Open. 2024;9:102195.
doi: 10.1016/jesmoop.2023.102195.

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Part 4 of 4: Applying Practical Protocols for Antiemetic Prophylax
Do They Differ Depending on ADC?

Karin Jordan, MD, PhD

Head of Hematology, Oncology and Palliative Care
Ernst von Bergmann Hospital Potsdam

Potsdam, Germany

Professor of Medicine

University of Heidelberg

Heidelberg, Germany

Copyright © 2010-2024, PeerVoi

23. PeerVoice

Karin Jordan, MD, PhD, has a financial interest/relationship or affiliation in
the form of:

Consultant for AstraZeneca and Daiichi Sankyo Company, Limited.
Advisory Board for Helsinn Healthcare SA.

www.peervoice.com/NFQ870 Copyright © 2010-2024, PeerVoice

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Mila: 64-Year-Old Woman With HER2+ mBC

+ Jan 2023: Diagnosed with + Docetaxel + trastuzumab-pertuzumab (THP)
HER2-positive/HR-negative for 18 mo until disease progression (PD)
mBC + PD: June 2024
| NH on Second-Line Therapy

+ No previous serious medical history + T-DXd (5.4 mg/kg Q3W)
- Father had and died from mCRC

What needs to be done prior to treatmen

» A possible option recommended by the NCCN guidelines is the use of:

+ Several options are available
— Olanzapine, oral NEPA, and oral dexamethasone on day of treatment

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MASCC/ESMO Guidelines: Acute and Delayed Emesis

Prevention

Acute Emesis Prevention for SG and T-DXd

Antiemetics
5-HT3 RA + 5 + aan
Ondansetron E au oo
Granisetron BIER!
Netupitant®
Dolasetron

Fosnetupitant®

Palonosetron Rolapitant

Delayed Emesis Prevention for SG and T-DXd

+ No steroid (or other antiemetic) should be routinely administered after day 1
+ If aprepitant 125 mg is used in day 1, then aprepitant 80 mg x 1 should be administered days 2-3

® Administered with palonosetron as part of the fixed-dose combination agent NEPA.

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NCCN Guidelines: Acute and Delayed Emesis Prevention

1. Olanzapine Olanzapine 1 NK-IRA 1. Aprepitant®
i 2. Palonosetron 2. 5-HT3RA | 2. Dexa

. 5-HT3 RA 3. Dexa

|. Dexa

Olanzapine

Day land
Days

+ Dolasetron: 100 mg PO once + Aprepitant:
5-10 mg PO once + Granisetron: 10 mg SQ once, or + Aprepitant:

2 mg PO once, or 0.01 mg/kg (max + Fosaprepitant: 150 mg IV once
Img) IV once, or 3.1 mg/24-h + Netupitant 300 mg / palonosetron 0.5 mg (available as
transdermal patch applied 24-48 h fixed combination product only) PO once
prior to first dose of anticancer + Fosnetupitant: 235 mg / palonosetron 0.25 mg
12mgPO/IVonce therapy (available as fixed combination product only) IV once
+ Ondansetron: 16-24 mg PO once, — * Rolapitant:180 mg PO once

Ban 025
8mgPO/IVonce + Palonosetron: 0.25 mg IV once 1
+ Aprepitant: 80 mg PO once®
*1f aprepitant PO is used on day 1.

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Abbreviations and References

Mila: 64-Year-Old Woman With HER2+ mBC

Abbreviation(s): mBC: metastatic breast cancer; mCRC: metastatic colorectal cancer; NCCN: National Comprehensive
Cancer Network; NEPA: netupitant and palonosetron; Q3W: every 3 weeks; T-DXd: trastuzumab deruxtecan.

MASCC/ESMO Guidelines: Acute and Delayed Emesis Prevention

Abbreviation(s): 5-HT3: serotonin; DEX: dexamethasone; ESMO: European Society for Medical Oncology;

MASCC: Multinational Association of Supportive Care in Cancer; NK-1: neurokinin 1; RA: receptor antagonist;

SG: sacituzumab govitecan.

Reference(s): Herrstedt J; participants of the MASCC/ESMO Consensus Conference 2022. ESMO Open. 2024;9:102195.
doi: 10.1016/j.esmoop.2023.102195.

NCCN Guidelines: Acute and Delayed Emesis Prevention

Abbreviation(s): PO: per os (by mouth).
Reference(s): Ettinger DS et al. NCCN Clinical Practice Guidelines in Oncology: Antiemesis; Version 1.2024.

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