When They Need More Than Trastuzumab: Deciding on What’s Next for Patients With HER2+ Gastric Cancer
PeerVoice
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Sep 13, 2024
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About This Presentation
Elizabeth Smyth, MD, FRCP, discusses gastric cancer in this CE activity titled "When They Need More Than Trastuzumab: Deciding on What’s Next for Patients With HER2+ Gastric Cancer." For the full presentation, please visit us at www.peervoice.com/SKB870.
Slide Content
PeerVoice
When They Need More Than Trastuzumab: Deciding on What's
Next for Patients With HER2+ Gastric Cancer
Learning Objectives
Discuss the need for early identification of relapse or disease progression in
patients with HER2+ gastric/gastroesophageal junction (GEJ) cancer who are
receiving HER2-targeted therapy
Identify how approved and investigational antibody-drug conjugate (ADC)
therapies for HER2+ gastric/GEJ cancer are differentiated, based on clinical data
and line of therapy
Explain the rationale for retesting HER2-positivity in patients with gastric/GEJ
cancer who have progressed on HER2-targeted therapy
Propose evidence-based treatment plans for patients with HER2+ gastric/GEJ
cancer who have progressed on HER2-targeted therapy, based on patient and
disease characteristics
PeerVoice is an EBAC* accredited provider since 2022
www.peervoice.com/SKB870 ight © 2010-2024, PeerVoice
When They Need More Than Trastuzumab: Deciding on What's
Next for Patients With HER2+ Gastric Cancer
Learning Objectives
Discuss the need for early identification of relapse or disease progression in
patients with HER2+ gastric/gastroesophageal junction (GEJ) cancer who are
receiving HER2-targeted therapy
Identify how approved and investigational antibody-drug conjugate (ADC)
therapies for HER2+ gastric/GEJ cancer are differentiated, based on clinical data
and line of therapy
Explain the rationale for retesting HER2-positivity in patients with gastric/GEJ
cancer who have progressed on HER2-targeted therapy
Propose evidence-based treatment plans for patients with HER2+ gastric/GEJ
cancer who have progressed on HER2-targeted therapy, based on patient and
disease characteristics
PeerVoice is an EBAC* accredited provider since 2022
www.peervoice.com/SKB870 ight © 2010-2024, PeerVoice
PeerVoice
Part 1 of 5: The Criticality of Taking Prompt Action in Patients
With Progression of HER2+ Gastric Cancer
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 1 of 5: The Criticality of Taking Prompt Action in Patients
With Progression of HER2+ Gastric Cancer
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
PeerVoice
HER2 in Gastric Cancer: Heterogeneity
As HER2-
Sp Rom
HER2+ Cells in IHC 3+ Patients > > q 2
Cells, % <10 10-30 31-79 280 eet
A B:HER2-
hetero
Patients,% 3 27 a 39 | ®
10 mPFS mos
Homo-HER2: 10.8 mo (95% CI, 6.9-19.4) Homo-HER2: 29.3 mo (95% Cl, 20.5-NR)
08 Hetero-HER2: 6.1 mo (95% Cl, 5.3-8.2) 08 Hetero-HER2: 14.4 mo (95% Cl, 11.4-17.8)
HR: 0.47 (95% Cl, 0.29-0.77) HR: 0.35 (95% Cl, 0.20-0.61)
y 06 03 os P<001
fo}
04 04
02 02
00 00
o 10 20 30 40 O 10 20 30 40 50 60
Time, mo Time, mo
www.peervoice.com/SKB870
Copyright © 2010-2024, PeerVoice
HER2 in Gastric Cancer: Heterogeneity
As HER2-
Sp Rom
HER2+ Cells in IHC 3+ Patients > > q 2
Cells, % <10 10-30 31-79 280 eet
A B:HER2-
hetero
Patients,% 3 27 a 39 | ®
10 mPFS mos
Homo-HER2: 10.8 mo (95% CI, 6.9-19.4) Homo-HER2: 29.3 mo (95% Cl, 20.5-NR)
08 Hetero-HER2: 6.1 mo (95% Cl, 5.3-8.2) 08 Hetero-HER2: 14.4 mo (95% Cl, 11.4-17.8)
HR: 0.47 (95% Cl, 0.29-0.77) HR: 0.35 (95% Cl, 0.20-0.61)
y 06 03 os P<001
fo}
04 04
02 02
00 00
o 10 20 30 40 O 10 20 30 40 50 60
Time, mo Time, mo
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Copyright © 2010-2024, PeerVoice
PeerVoice
HER2 in Gastric Cancer: Dynamic Changes With Treatment
HER2 Status IHC and/or FISH of Tumour Tissue Before and After First-Line Trastuzumab
Treatment and Tumour Response on First- and Second-Line Treatment
Paclitaxel Paclitaxel + Trastuzumab
(n=10) (n=8)
= Ill 3+ for IHC or positive for FISH
HO botore ess Mery ‘or circulating amplification
FISH before first-line therapy | a E EE ORC EE D Rent
TUE Taper Hotere rest A — o — EBER AE rc:
O for IHC or negative for FISH
IHC after first-line therapy or circulating HER2 DNA amplification
FISH after first-line therapy.
Ml D not evaluated
able
Crevlatng HERZ ONA amptticstion ME MN DE
Lee]
ES a
Stable disease or non-CR/non-PD
PD
Copyright © 2010-2024, PeerVoice
HER2 in Gastric Cancer: Dynamic Changes With Treatment
HER2 Status IHC and/or FISH of Tumour Tissue Before and After First-Line Trastuzumab
Treatment and Tumour Response on First- and Second-Line Treatment
Paclitaxel Paclitaxel + Trastuzumab
(n=10) (n=8)
= Ill 3+ for IHC or positive for FISH
HO botore ess Mery ‘or circulating amplification
FISH before first-line therapy | a E EE ORC EE D Rent
TUE Taper Hotere rest A — o — EBER AE rc:
O for IHC or negative for FISH
IHC after first-line therapy or circulating HER2 DNA amplification
FISH after first-line therapy.
Ml D not evaluated
able
Crevlatng HERZ ONA amptticstion ME MN DE
Lee]
ES a
Stable disease or non-CR/non-PD
PD
Copyright © 2010-2024, PeerVoice
PeerVoice
ER2 Status: Why Should Patients Be Retested?
High degree of tumour
heterogeneity; HER2 may
be expressed differently
in primary and metastatic
tumour sites
Which Patients Should Be Retested?
All patients with HER2+ disease after progression on
first-line therapy (when a biopsy is safe and feasible)
Copyright © 2010-2024, PeerVoice
ER2 Status: Why Should Patients Be Retested?
High degree of tumour
heterogeneity; HER2 may
be expressed differently
in primary and metastatic
tumour sites
Which Patients Should Be Retested?
All patients with HER2+ disease after progression on
first-line therapy (when a biopsy is safe and feasible)
Copyright © 2010-2024, PeerVoice
PeerVoice
Determining HER2 Status
sé
pa
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
Determining HER2 Status
sé
pa
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PeerVoice
Abbreviations and References
HER2 in Gastric Cancer: Heterogeneity
Abbreviation(s): HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry.
Reference(s): Lordick F, Janjigian YY. Nat Rev Clin Oncol. 2016:13(6):348-60.
Van Cutsem E et al. Gastric Cancer. 2015;18:476-84.
Yogi S et al. Gastric Cancer. 2019;22:518-525.
HER2 in Gastric Cancer: Dynamic Changes With Treatment
Abbreviation(s): CR: complete response; FISH: fluorescence in situ hybridisation;
response.
Reference(s): Pietrantonio F et al. Int J Cancer. 2016;139(12):2859-2864.
Makiyma et al. J Clin Oncol, 2020;38:1919-1927.
D: progressive disease; PR: partial
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Abbreviations and References
HER2 in Gastric Cancer: Heterogeneity
Abbreviation(s): HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry.
Reference(s): Lordick F, Janjigian YY. Nat Rev Clin Oncol. 2016:13(6):348-60.
Van Cutsem E et al. Gastric Cancer. 2015;18:476-84.
Yogi S et al. Gastric Cancer. 2019;22:518-525.
HER2 in Gastric Cancer: Dynamic Changes With Treatment
Abbreviation(s): CR: complete response; FISH: fluorescence in situ hybridisation;
response.
Reference(s): Pietrantonio F et al. Int J Cancer. 2016;139(12):2859-2864.
Makiyma et al. J Clin Oncol, 2020;38:1919-1927.
D: progressive disease; PR: partial
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
PeerVoice
Abbreviations and References (Cont'd)
HER2 Status: Why Should Patients Be Retested?
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
Determining HER2 Status
Abbreviation(s): ISH: in situ hybridisation.
Reference(s): Bartley AN et al. J Clin Oncol. 2017;35:446-464.
Viale G. HER2 in Gastric Cancer: ESMO Biomarker Factsheet. Oncology Pro. https://oncologypro.esmo.org/education-
library/factsheets-on-biomarkers/her2-in-gastric-cancer. Accessed 29 August 2024.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
Abbreviations and References (Cont'd)
HER2 Status: Why Should Patients Be Retested?
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
Determining HER2 Status
Abbreviation(s): ISH: in situ hybridisation.
Reference(s): Bartley AN et al. J Clin Oncol. 2017;35:446-464.
Viale G. HER2 in Gastric Cancer: ESMO Biomarker Factsheet. Oncology Pro. https://oncologypro.esmo.org/education-
library/factsheets-on-biomarkers/her2-in-gastric-cancer. Accessed 29 August 2024.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
PeerVoice
Part 2 of 5: Treatment Beyond First-Line for Patients
With HER2+ Gastric Cancer: The An
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 2 of 5: Treatment Beyond First-Line for Patients
With HER2+ Gastric Cancer: The An
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
PeerVoice
Anti-HER2 Therapy for HER2-High Advanced Gastric Cancer
ESMO Gastric Cancer Guidelines Japanese Gastric NCCN Gastric Cancer Guidelines
SE systeme therapy for unresectabeIocaly-adrarces, recurrent, or
metastatic disease
(here local therapy not indicated)
‘Advancedlmetastaic urresectabe sense
ars First-Line First-Line: Oxaliplatin is preferred over cisplatin due to
sm-foropyrnidine doubt CHT lower toxicity
2 HER2+
> SFU+cisplatin + || HERZ overexpression-positive
Let + Fluoropyrimidine? and oxaliplatin and trastuzumab
“SFO OK + Flucropyrimidine* and oxaliplatin and trastuzumab
asuma and pembrolizumab
latin and trastuzumab
Second-Line + Fluoropyrimidine* and cisplatin and trastuzumab
and pembrolizumab
De Een o HER2+
and POC Consider combo of
7 rastuzumab + CHT
in the case of no
prior trastuzumab
HERZ overexpression.
+ Fluoropyrimidine”, oxaliplatin, and nivolumab (PD-L1
CPS 25)
+ Fluoropyrimidine* and oxaliplatin
+ Fluoropyrimidine* and cisplatin
Roda! essetien too considered
nin select casos
* Fluorouracil or capecitabine
Anti-HER2 therapy is recommended by all international gastric cancer guidelines
www.peervoice.com/SKB870 Copyright 6 2010-2024, PeerVoice
Anti-HER2 Therapy for HER2-High Advanced Gastric Cancer
ESMO Gastric Cancer Guidelines Japanese Gastric NCCN Gastric Cancer Guidelines
SE systeme therapy for unresectabeIocaly-adrarces, recurrent, or
metastatic disease
(here local therapy not indicated)
‘Advancedlmetastaic urresectabe sense
ars First-Line First-Line: Oxaliplatin is preferred over cisplatin due to
sm-foropyrnidine doubt CHT lower toxicity
2 HER2+
> SFU+cisplatin + || HERZ overexpression-positive
Let + Fluoropyrimidine? and oxaliplatin and trastuzumab
“SFO OK + Flucropyrimidine* and oxaliplatin and trastuzumab
asuma and pembrolizumab
latin and trastuzumab
Second-Line + Fluoropyrimidine* and cisplatin and trastuzumab
and pembrolizumab
De Een o HER2+
and POC Consider combo of
7 rastuzumab + CHT
in the case of no
prior trastuzumab
HERZ overexpression.
+ Fluoropyrimidine”, oxaliplatin, and nivolumab (PD-L1
CPS 25)
+ Fluoropyrimidine* and oxaliplatin
+ Fluoropyrimidine* and cisplatin
Roda! essetien too considered
nin select casos
* Fluorouracil or capecitabine
Anti-HER2 therapy is recommended by all international gastric cancer guidelines
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ToGA and Keynote-811: Efficacy
10
os
os
07
os
04
Trastuzumab +
os Chemotherapy
02
oa
Survival Probability
ie
|
111, ¡138 chemotherapy alone
0 2 & 6 8 10 12 14 16 18 20 2 24 26 28 30 32 34 36
Time, mo
+ Addition of trastuzumab improved response rate, PFS, and OS
+ Trastuzumab is most effective in IHC 3+ or IHC 2+ FISH-positive disease
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ToGA and Keynote-811: Efficacy
10
os
os
07
os
04
Trastuzumab +
os Chemotherapy
02
oa
Survival Probability
ie
|
111, ¡138 chemotherapy alone
0 2 & 6 8 10 12 14 16 18 20 2 24 26 28 30 32 34 36
Time, mo
+ Addition of trastuzumab improved response rate, PFS, and OS
+ Trastuzumab is most effective in IHC 3+ or IHC 2+ FISH-positive disease
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DESTINY-Gastric01: Study Design
Multicentre, open-label, randomised phase 2 study
Adult patients with HER2+
T-DXd 6.4 mg/kg, 3-wk cycles
locally advanced or Hales 2 Primary endpoint
metastatic gastric or GE) : ORR by ICR (RECIST
cancer that progressed on a He m v1.1)
> 2 prior regimens' pier
(N= 188) TPC: withdrawal
Irinotecan 150 mg/m? Q2W or Secondary endpoints
2
Paclitaxel 80 mg/m? on days 1, 8, OS (key), DoR, PFS,
Stratification ou DCR, confirmed ORR,
Region (Japan vs Korea) (n= 62) safety
ECOG PS (0 vs 1),
HER2 status (IHC 3+ vs IHC 2+/1SH+)
+ HER2+ based on IHC 3+ or IHC 2+/ISH+ according to ASCO/CAP guidelines
+ Prior regimens included fluoropyrimidine, a platinum agent, and trastuzumab or approved biosimilar
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DESTINY-Gastric01: Study Design
Multicentre, open-label, randomised phase 2 study
Adult patients with HER2+
T-DXd 6.4 mg/kg, 3-wk cycles
locally advanced or Hales 2 Primary endpoint
metastatic gastric or GE) : ORR by ICR (RECIST
cancer that progressed on a He m v1.1)
> 2 prior regimens' pier
(N= 188) TPC: withdrawal
Irinotecan 150 mg/m? Q2W or Secondary endpoints
2
Paclitaxel 80 mg/m? on days 1, 8, OS (key), DoR, PFS,
Stratification ou DCR, confirmed ORR,
Region (Japan vs Korea) (n= 62) safety
ECOG PS (0 vs 1),
HER2 status (IHC 3+ vs IHC 2+/1SH+)
+ HER2+ based on IHC 3+ or IHC 2+/ISH+ according to ASCO/CAP guidelines
+ Prior regimens included fluoropyrimidine, a platinum agent, and trastuzumab or approved biosimilar
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DESTINY-Gastric01: Efficacy
PFS
Patients, %
Patients, %
0 3 6 9 2 15 18 21 24 0 3 6 9 2 15 18 2 24
Time, mo Time, mo
Response d (n = 119)
ORR, % 51 14
Jan 15, 2021: T-DXd was FDA-approved for patients with locally advanced or metastatic HER2+ gastric or GE!
adenocarcinoma who have received a prior trastuzumab-based regimen
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DESTINY-Gastric01: Efficacy
PFS
Patients, %
Patients, %
0 3 6 9 2 15 18 21 24 0 3 6 9 2 15 18 2 24
Time, mo Time, mo
Response d (n = 119)
ORR, % 51 14
Jan 15, 2021: T-DXd was FDA-approved for patients with locally advanced or metastatic HER2+ gastric or GE!
adenocarcinoma who have received a prior trastuzumab-based regimen
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DESTINY-Gastric02: Study Design and Efficacy
Unresectable or metastatic gastric or GEI
cancer, HER2+ (defined as IHC 3+ or IHC
2+/15H+) on biopsy after progression on gp
first-line trastuzumab-containing regimen, 6.4 mg/kg Q3W
ECOG PS 0/1
(n=79) Primary endpoint:
confirmed ORR by ICR
012345678901 21345617 192072223
Response Assessment by Time, mo
cr
contrmesors(o) | sn araane) (sh 0,308 834)
Confirmed best OR, % (n)
ck 3361 ET)
PR 34.3 (27) 36.7 (29)
so 064) 3200 012s 4507 ION
Fo 265 (13) 165 (3) Time, mo
NE 25 (2) 2.5(2)
81.0 (64) 81.0 (64) Dec. 19, 2022: T-DXd approved in the EU as a monotherapy
coated Ol (95% Cl, 70.6-89.0) (95% Cl, 70.6-89.0) for the treatment of adult patients with advanced HER2+
Median DoR,mo 8:1 (95% Cl, 4.1-NE) 8.1(959 Cl, 4.NE) gastric or GE) adenocarcinoma who have received a pi
Median TTR, mo 1.8 (95% 0,142) LA (95% C1 14-26) trastuzumab-based regimen
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DESTINY-Gastric02: Study Design and Efficacy
Unresectable or metastatic gastric or GEI
cancer, HER2+ (defined as IHC 3+ or IHC
2+/15H+) on biopsy after progression on gp
first-line trastuzumab-containing regimen, 6.4 mg/kg Q3W
ECOG PS 0/1
(n=79) Primary endpoint:
confirmed ORR by ICR
012345678901 21345617 192072223
Response Assessment by Time, mo
cr
contrmesors(o) | sn araane) (sh 0,308 834)
Confirmed best OR, % (n)
ck 3361 ET)
PR 34.3 (27) 36.7 (29)
so 064) 3200 012s 4507 ION
Fo 265 (13) 165 (3) Time, mo
NE 25 (2) 2.5(2)
81.0 (64) 81.0 (64) Dec. 19, 2022: T-DXd approved in the EU as a monotherapy
coated Ol (95% Cl, 70.6-89.0) (95% Cl, 70.6-89.0) for the treatment of adult patients with advanced HER2+
Median DoR,mo 8:1 (95% Cl, 4.1-NE) 8.1(959 Cl, 4.NE) gastric or GE) adenocarcinoma who have received a pi
Median TTR, mo 1.8 (95% 0,142) LA (95% C1 14-26) trastuzumab-based regimen
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DESTINY-Gastric01 and DESTINY-Gastric02: Safety
DESTINY-Gastrico1
neutrophil count
Decreased appetite
‘Anaemia
Any
Grade
[Grade 3/4
35 (44)
28(35)
5(6)
04)
Decreased platelet
‘count
Decreased white cell
count
Malaise
Diarrhoea
Vomiting
Constipation
Pyrexia
Alopecia
Fatigue
Decreased
lymphocyte count
www.peervoice.com/SKB870
35
32
32
23
16
15
24
4765) 6 (8) o o
ss) 20) o o
Fotigue 30(88) 3) o o
Diarrhoea 28 (35) 10) o o
Decreased weight 25(32) 34) o o
Constipation 23 (29) o o o
Decreased appetite 22(28) 416) o o
Anaemia 19 (24) mia) o o
Alopecia 19 (24) o o o
Decre elt: wits) 26) o o
|| o o
Hypokalaemia 12(15) o 10 o
Abdominal pain 10) 203) o o
Asthenia 114) 10 o o
Copyright © 2010-2024, PeerVoice
DESTINY-Gastric01 and DESTINY-Gastric02: Safety
DESTINY-Gastrico1
neutrophil count
Decreased appetite
‘Anaemia
Any
Grade
[Grade 3/4
35 (44)
28(35)
5(6)
04)
Decreased platelet
‘count
Decreased white cell
count
Malaise
Diarrhoea
Vomiting
Constipation
Pyrexia
Alopecia
Fatigue
Decreased
lymphocyte count
www.peervoice.com/SKB870
35
32
32
23
16
15
24
4765) 6 (8) o o
ss) 20) o o
Fotigue 30(88) 3) o o
Diarrhoea 28 (35) 10) o o
Decreased weight 25(32) 34) o o
Constipation 23 (29) o o o
Decreased appetite 22(28) 416) o o
Anaemia 19 (24) mia) o o
Alopecia 19 (24) o o o
Decre elt: wits) 26) o o
|| o o
Hypokalaemia 12(15) o 10 o
Abdominal pain 10) 203) o o
Asthenia 114) 10 o o
Copyright © 2010-2024, PeerVoice
PeerVoice
Ongoing HER2 Targeting ADCs in Advanced Gastric Cancer
= Primary
Study Phase Drug Therapy Line | Remark Status Endpoint
Ne TOs Gates Trastuzumab vs ram +
DESTINY- 3 dermilecan Second-line acli Recruiting os
Gastric04 Ps
Disitamab p + toripalimab A
NCT06078982 1 vedotin 2 second-line HER2-low Recruiting ORR
Trastuzumab r +ICl, +X, A Dose escalation,
NCT05671822 1b/2 rezetecan 2 second-line + CAPOX Recruiting ORR
Zanidatamab HER Safety,
NCT03821233 A a Last-line advanced Active és
zovodotin diras tolerability
HER+
NCT03255070 À ARX788 Last-line advanced Active Safety, ORR
solid tumours
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Ongoing HER2 Targeting ADCs in Advanced Gastric Cancer
= Primary
Study Phase Drug Therapy Line | Remark Status Endpoint
Ne TOs Gates Trastuzumab vs ram +
DESTINY- 3 dermilecan Second-line acli Recruiting os
Gastric04 Ps
Disitamab p + toripalimab A
NCT06078982 1 vedotin 2 second-line HER2-low Recruiting ORR
Trastuzumab r +ICl, +X, A Dose escalation,
NCT05671822 1b/2 rezetecan 2 second-line + CAPOX Recruiting ORR
Zanidatamab HER Safety,
NCT03821233 A a Last-line advanced Active és
zovodotin diras tolerability
HER+
NCT03255070 À ARX788 Last-line advanced Active Safety, ORR
solid tumours
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Abbreviations and References
Anti-HER2 Therapy for HER2-High Advanced Gastric Cancer
Abbreviation(s): 5-FU: 5-fluorouracil; ChT: chemotherapy; CPS: combined positive score; dMMR: deficient mismatch
repair; FOLFOX: folinic acid, fluorouracil, and oxaliplatin; HER2: human epidermal growth factor receptor 2; ICI: immune
checkpoint inhibitor; MSI microsatellite instability; NCCN: National Comprehensive Cancer Network; PD: progressive
disease.
Reference(s): Lordick F et al. Ann Oncol, 2022;33:1005-1020.
Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric
Cancer. 2023:261-25.
NCCN Guidelines. Gastric Cancer. Version 4.2024. https://www.ncen org/professionals/physician_gls/paf/gastric.paf.
Accessed 29 August 2024.
ToGA and Keynote-811: Efficacy
Abbreviation(s): FISH: fluoresence in situ hybridisation; IHC: immunohistochemistry.
Reference(s): Bang YJ et al. Lancet. 2010;376:687-697.
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Abbreviations and References
Anti-HER2 Therapy for HER2-High Advanced Gastric Cancer
Abbreviation(s): 5-FU: 5-fluorouracil; ChT: chemotherapy; CPS: combined positive score; dMMR: deficient mismatch
repair; FOLFOX: folinic acid, fluorouracil, and oxaliplatin; HER2: human epidermal growth factor receptor 2; ICI: immune
checkpoint inhibitor; MSI microsatellite instability; NCCN: National Comprehensive Cancer Network; PD: progressive
disease.
Reference(s): Lordick F et al. Ann Oncol, 2022;33:1005-1020.
Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric
Cancer. 2023:261-25.
NCCN Guidelines. Gastric Cancer. Version 4.2024. https://www.ncen org/professionals/physician_gls/paf/gastric.paf.
Accessed 29 August 2024.
ToGA and Keynote-811: Efficacy
Abbreviation(s): FISH: fluoresence in situ hybridisation; IHC: immunohistochemistry.
Reference(s): Bang YJ et al. Lancet. 2010;376:687-697.
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Abbreviations and References (Cont'd)
DESTINY-GastricOI: Study Design
Abbreviation(s): CAP: College of American Pathologists; DCR: disease control rate; DoR: duration of response;
GEL): gastroesophageal junction; ICR: independent central review; ISH: in situ hybridisation; ORR: overall response rate;
PD: progressive disease; PS: performance status; RECIST: Response Evaluation Criteria in Solid Tumors;
T-DXd: trastuzumab deruxtecan; TPC: treatment of physician's choice.
Reference(s): Shitara K et al. N Engl J Med. 2020;382:2419-2430.
DESTINY-GastricOI: Efficacy
Reference(s): Shitara K et al. N Engl J Med. 2020;382:2419-2430.
DESTINY-GastricO2: Study Design and Efficacy
Abbreviation(s): CR: complete response; NE: not evaluable; OR: objective response; PR: partial response; SD: stable
disease; TTR: time to response.
Reference(s): Ku G et al. Ann Oncol. 2022;33(suppl_7):S555-S580.
Van Cutsem E et al. Lancet Oncol. 2023;24:744-756.
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Abbreviations and References (Cont'd)
DESTINY-GastricOI: Study Design
Abbreviation(s): CAP: College of American Pathologists; DCR: disease control rate; DoR: duration of response;
GEL): gastroesophageal junction; ICR: independent central review; ISH: in situ hybridisation; ORR: overall response rate;
PD: progressive disease; PS: performance status; RECIST: Response Evaluation Criteria in Solid Tumors;
T-DXd: trastuzumab deruxtecan; TPC: treatment of physician's choice.
Reference(s): Shitara K et al. N Engl J Med. 2020;382:2419-2430.
DESTINY-GastricOI: Efficacy
Reference(s): Shitara K et al. N Engl J Med. 2020;382:2419-2430.
DESTINY-GastricO2: Study Design and Efficacy
Abbreviation(s): CR: complete response; NE: not evaluable; OR: objective response; PR: partial response; SD: stable
disease; TTR: time to response.
Reference(s): Ku G et al. Ann Oncol. 2022;33(suppl_7):S555-S580.
Van Cutsem E et al. Lancet Oncol. 2023;24:744-756.
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Abbreviations and References (Cont'd)
DESTINY-GastricO1 and DESTINY-GastricO2: Safety
Abbreviation(s): TRAE: treatment-related adverse event.
Reference(s): Shitara K et al. N Engl J Med. 2020;382:2419-2430.
Ku G et al. Ann Oncol. 2022;33(suppl_7):S555-S580.
Van Cutsem E et al. Lancet Oncol. 2023;24:744-756.
Ongoing HER2 Targeting ADCs in Advanced Gastric Cancer
Abbreviation(s): ADC: antibody-drug conjugate; CAPOX: capecitabine and oxaliplatin; pacli: paclitaxel;
ram: ramucirumab; X: capecitabine.
Reference(s): Scheck MK et al. Cancers. 2024;16:1336.
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Abbreviations and References (Cont'd)
DESTINY-GastricO1 and DESTINY-GastricO2: Safety
Abbreviation(s): TRAE: treatment-related adverse event.
Reference(s): Shitara K et al. N Engl J Med. 2020;382:2419-2430.
Ku G et al. Ann Oncol. 2022;33(suppl_7):S555-S580.
Van Cutsem E et al. Lancet Oncol. 2023;24:744-756.
Ongoing HER2 Targeting ADCs in Advanced Gastric Cancer
Abbreviation(s): ADC: antibody-drug conjugate; CAPOX: capecitabine and oxaliplatin; pacli: paclitaxel;
ram: ramucirumab; X: capecitabine.
Reference(s): Scheck MK et al. Cancers. 2024;16:1336.
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PeerVoice
Part 3 of 5: And Still They Progress: What Impacts the Next Therapeutic
Decision in Patients With Advanced HER2+ Gastric Cancer - Case 1
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
# Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 3 of 5: And Still They Progress: What Impacts the Next Therapeutic
Decision in Patients With Advanced HER2+ Gastric Cancer - Case 1
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
# Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
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PeerVoice
A 69-Year-Old Woman HER2+ GEJ Cancer
Initial Presentation
Past medical history: hypertension, hypercholesterolaemia
Medication: omeprazole, amlodipine, atorvastatin
Dysphagia lasting 2 months
Endoscopy: malignant-appearing circumferential mass
arising at the GEJ
CT: T3N1 gastroesophageal tumour with 2 liver metastases
Histology: adenocarcinoma, HER2 3+, MMR intact,
PD-L1, CPS 3
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A 69-Year-Old Woman HER2+ GEJ Cancer
Initial Presentation
Past medical history: hypertension, hypercholesterolaemia
Medication: omeprazole, amlodipine, atorvastatin
Dysphagia lasting 2 months
Endoscopy: malignant-appearing circumferential mass
arising at the GEJ
CT: T3N1 gastroesophageal tumour with 2 liver metastases
Histology: adenocarcinoma, HER2 3+, MMR intact,
PD-L1, CPS 3
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A 69-Year-Old Woman With HER2+ GEJ Cancer (Co
Initial Treatment
Commenced CAPOX, trastuzumab plus pembrolizumab
After 3 months: excellent response on CT
After 6 months: chemotherapy was discontinued, trastuzumab and
pembrolizumab were maintained
After 15 months: increasing dysphagia
Endoscopy and CT showed progression in
primary metastases
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A 69-Year-Old Woman With HER2+ GEJ Cancer (Co
Initial Treatment
Commenced CAPOX, trastuzumab plus pembrolizumab
After 3 months: excellent response on CT
After 6 months: chemotherapy was discontinued, trastuzumab and
pembrolizumab were maintained
After 15 months: increasing dysphagia
Endoscopy and CT showed progression in
primary metastases
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A 69-Year-Old Woman With HER2+ GEJ Cancer (Co
Treatment After Progression
Second-line treatment:
+ Biopsy of primary tumour: retained HER2 3+ status
* Started T-DXd with resolution of symptoms
* Remains on treatment
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A 69-Year-Old Woman With HER2+ GEJ Cancer (Co
Treatment After Progression
Second-line treatment:
+ Biopsy of primary tumour: retained HER2 3+ status
* Started T-DXd with resolution of symptoms
* Remains on treatment
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Abbreviations and References
A69-Year-Old Woman With HER2+ GEJ Cancer
Abbreviation(s): CPS: combined positive score; GEJ: gastroesophageal junction; HER2: human epidermal growth factor
receptor 2; MMR: mismatch repair.
Reference(s): Personal communic:
: Elizabeth Smyth, MD, FRCP; August 2024.
A 69-Year-Old Woman With HER2+ GEJ Cancer (Cont'd)
Abbreviation(s): CAPOX: capecitabine and oxaliplatin.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
A 69-Year-Old Woman With HER2+ GEJ Cancer (Cont'd)
Abbreviation(s): T-DXd: trastuzumab deruxtecan.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
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Abbreviations and References
A69-Year-Old Woman With HER2+ GEJ Cancer
Abbreviation(s): CPS: combined positive score; GEJ: gastroesophageal junction; HER2: human epidermal growth factor
receptor 2; MMR: mismatch repair.
Reference(s): Personal communic:
: Elizabeth Smyth, MD, FRCP; August 2024.
A 69-Year-Old Woman With HER2+ GEJ Cancer (Cont'd)
Abbreviation(s): CAPOX: capecitabine and oxaliplatin.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
A 69-Year-Old Woman With HER2+ GEJ Cancer (Cont'd)
Abbreviation(s): T-DXd: trastuzumab deruxtecan.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
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PeerVoice
Part 4 of 5: And Still They Progress: What Impacts the Next Therapeutic
Decision in Patients With Advanced HER2+ Gastric Cancer - Case 2
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 4 of 5: And Still They Progress: What Impacts the Next Therapeutic
Decision in Patients With Advanced HER2+ Gastric Cancer - Case 2
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
PeerVoice
82
ar-Old Man With Advanced HER2+ Gastric Cancer
Initial Presentation
Past medical history: prostatism, arthritis, CKD
+ Abdominal pain and weight loss x 3 months
* Medication: tamulosin, paracetamol
* Social history: industrial worker, dust exposure
+ Endoscopy: tumour in the stomach antrum
+ CT: T4N1 stomach cancer with peritoneal metastases
+ Histology: adenocarcinoma, HER2 2+, FISH positive,
MMR intact, PD-L1, CPS O
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82
ar-Old Man With Advanced HER2+ Gastric Cancer
Initial Presentation
Past medical history: prostatism, arthritis, CKD
+ Abdominal pain and weight loss x 3 months
* Medication: tamulosin, paracetamol
* Social history: industrial worker, dust exposure
+ Endoscopy: tumour in the stomach antrum
+ CT: T4N1 stomach cancer with peritoneal metastases
+ Histology: adenocarcinoma, HER2 2+, FISH positive,
MMR intact, PD-L1, CPS O
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82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Initial Treatment
Commenced FOLFOX and trastuzumab
+ Good initial clinical response
+ After 6 months: increased abdominal discomfort with r
bloating
* CT: progressive disease
* Repeat biopsy: HER2 2+, FISH negative
aa
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82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Initial Treatment
Commenced FOLFOX and trastuzumab
+ Good initial clinical response
+ After 6 months: increased abdominal discomfort with r
bloating
* CT: progressive disease
* Repeat biopsy: HER2 2+, FISH negative
aa
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PeerVoice
82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Treatment After Progression
* HER2 status: HER2 2+ FISH negative
+ Risk factors for TdXD toxicity: CKD, lung changes
+ Commenced paclitaxel and ramucirumab
=
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82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Treatment After Progression
* HER2 status: HER2 2+ FISH negative
+ Risk factors for TdXD toxicity: CKD, lung changes
+ Commenced paclitaxel and ramucirumab
=
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Abbreviations and References
82-Year-Old Man With Advanced HER2+ Gastric Cancer
Abbreviation(s): CKD: chronic kidney disease; CPS: combined positive score; FISH: fluorescence in situ hybridisation;
HER2: human epidermal growth factor receptor 2; MMR: mismatch repair.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): FOLFOX: folinic acid, fluorouracil, and oxaliplatin.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): T-DXd: trastuzumab deruxtecan.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
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Abbreviations and References
82-Year-Old Man With Advanced HER2+ Gastric Cancer
Abbreviation(s): CKD: chronic kidney disease; CPS: combined positive score; FISH: fluorescence in situ hybridisation;
HER2: human epidermal growth factor receptor 2; MMR: mismatch repair.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): FOLFOX: folinic acid, fluorouracil, and oxaliplatin.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
82-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): T-DXd: trastuzumab deruxtecan.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
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PeerVoice
Part 5 of 5: And Still They Progress: What Impacts the Next Therapeutic
Decision in Patients With Advanced HER2+ Gastric Cancer - Case 3
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
Part 5 of 5: And Still They Progress: What Impacts the Next Therapeutic
Decision in Patients With Advanced HER2+ Gastric Cancer - Case 3
Elizabeth Smyth, MD, FRCP
Honorary Senior Researcher
University of Oxford
Consultant in Gastrointestinal Oncology
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Copyright © 2010-2024, PeerVoice
PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
Elizabeth Smyth, MD, FRCP, has a financial interest/relationship or affiliation in the
form of:
Consultant for Amal Therapeutics SA; Amgen Inc.; Astellas Pharma Inc.; AstraZeneca;
BeiGene; Bristol Myers Squibb Company; Celgene Corporation; Daiichi Sankyo
Company, Limited; F. Hoffmann-La Roche Ltd; Gritstone bio; Merck KGaA; Merck
Sharp & Dohme Corp. Novartis AG; Pfizer Inc.; SAl MedPartners; Servier SAS; T-
CypherBio; The My Personal Therapeutics Foundation; Turning Point Therapeutics,
Inc.; Viracta Therapeutics, Inc.; and Zymeworks Inc.
Grant/Research Support from AstraZeneca and Bristol Myers Squibb Company.
Speaker or participant in accredited CME/CPD for Amgen Inc.; Aptitude Health
Holdings, LLC; Astellas Pharma Inc.; AstraZeneca; BeiGene; Bristol Myers Squibb
Company; Daiichi Sankyo Company, Limited; F. Hoffmann-La Roche Ltd; FirstWord;
Imedex, Inc; Merck KGaA; Novartis AG; Pfizer Inc.; Servier SAS; Viracta Therapeutics,
Inc. and Zymeworks Inc.
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PeerVoice
46-Year-Old Man With Advanced HER2+ Gastric Cancer
Initial Presentation
Dysphagia and weight loss (10 kg)
+ 2019: diagnosed with HER2+ GEJ adenocarcinoma confirmed by
endoscopy
* Histology: adenocarcinoma, HER2+, MMR intact, | =
PD-L1, CPS 5 |
CT: T3N2 tumour with no metastases
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46-Year-Old Man With Advanced HER2+ Gastric Cancer
Initial Presentation
Dysphagia and weight loss (10 kg)
+ 2019: diagnosed with HER2+ GEJ adenocarcinoma confirmed by
endoscopy
* Histology: adenocarcinoma, HER2+, MMR intact, | =
PD-L1, CPS 5 |
CT: T3N2 tumour with no metastases
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46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Initial Treatment
Commenced FLOT chemotherapy
Surgery with resection (revealed tumour was T2NI, 2/37 lymph nodes
involved, HER2+)
4x cycles adjuvant FLOT chemotherapy
After 18 months: CT showed liver metastases
Commenced capecitabine/oxaliplatin + trastuzumab
After 4 months: liver metastases were reduced and
surgically resected, chemotherapy was paused
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46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Initial Treatment
Commenced FLOT chemotherapy
Surgery with resection (revealed tumour was T2NI, 2/37 lymph nodes
involved, HER2+)
4x cycles adjuvant FLOT chemotherapy
After 18 months: CT showed liver metastases
Commenced capecitabine/oxaliplatin + trastuzumab
After 4 months: liver metastases were reduced and
surgically resected, chemotherapy was paused
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46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Treatment After Progression
+ After 3 months: CT showed lymph node growth
* Biopsy was not possible due to blood vessel proximity
+ HER2 status: unknown
* Commenced paclitaxel + ramucirumab (initial response at 3 months)
+ After 8 months: lymph node growth at same site,
biopsy still not possible
+ Commenced trastuzumab deruxtecan
» After 3 months: good partial response
+ Remains on treatment ——
=3
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46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont’d)
Treatment After Progression
+ After 3 months: CT showed lymph node growth
* Biopsy was not possible due to blood vessel proximity
+ HER2 status: unknown
* Commenced paclitaxel + ramucirumab (initial response at 3 months)
+ After 8 months: lymph node growth at same site,
biopsy still not possible
+ Commenced trastuzumab deruxtecan
» After 3 months: good partial response
+ Remains on treatment ——
=3
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice
PeerVoice
Abbreviations and References
46-Year-Old Man With Advanced HER2+ Gastric Cancer
Abbreviation(s): CPS: combined positive score; GEJ: gastroesophageal junction; HER2: human epidermal growth factor
receptor 2; MMR: mismatch repair.
Reference(s): Personal communic:
: Elizabeth Smyth, MD, FRCP; August 2024.
46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): FLOT: fluorouracil, leucovorin, oxaliplatin, and docetaxel.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): T-DXd: trastuzumab deruxtecan.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice.
Abbreviations and References
46-Year-Old Man With Advanced HER2+ Gastric Cancer
Abbreviation(s): CPS: combined positive score; GEJ: gastroesophageal junction; HER2: human epidermal growth factor
receptor 2; MMR: mismatch repair.
Reference(s): Personal communic:
: Elizabeth Smyth, MD, FRCP; August 2024.
46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): FLOT: fluorouracil, leucovorin, oxaliplatin, and docetaxel.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
46-Year-Old Man With Advanced HER2+ Gastric Cancer (Cont'd)
Abbreviation(s): T-DXd: trastuzumab deruxtecan.
Reference(s): Personal communication: Elizabeth Smyth, MD, FRCP; August 2024.
www.peervoice.com/SKB870 Copyright © 2010-2024, PeerVoice.
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