Up Close and Personalizing Gastric Cancer Care: Precision Medicine With HER2-Targeted Therapies and Other Novel Agents

NCCN Guidelines: Gastric Cancer1
PRACTICE AID
Access the activity, “Up Close and Personalizing Gastric Cancer Care: Precision Medicine With
HER2-Targeted Therapies and Other Novel Agents,” at PeerView.com/JQB40
Unresectable locally advanced, locally recurrent,
or metastatic disease
Karnofsky PS ≥60% or
ECOG PS ≤2
Karnofsky PS <60% or
ECOG PS ≥3
Perform HER2, PD-L1, MSI by PCR/MMR by
ICH testing (if not done previously) if
metastatic adenocarcinoma is documented
or suspected
Best
supportive
care
HER2 All Others
Trastuzumab
• Add to first-line
chemotherapy for
HER2 overexpressing
metastatic
adenocarcinoma
• Combination with
fluoropyrimidine and
platinum agents
• Not recommended for
use with anthracyclines
First·Line Therapy
• Two-drug cytotoxic regimens are
preferred because of lower toxicity
• Three-drug cytotoxic regimens should
be reserved for medically fit patients
with good PS and access to frequent
toxicity evaluation
• Oxaliplatin is generally preferred over
cisplatin because of lower toxicity
Preferred Regimens
• Fluoropyrimidine (fluorouracil or
capecitabine) and oxaliplatin
• Fluoropyrimidine (fluorouracil or
capecitabine) and cisplatin
Performance Status
PalliativeManagement

NCCN Guidelines: Gastric Cancer1
PRACTICE AID
CPS: combined positive score; dMMR: deficient mismatch repair; ECOG: Eastern Cooperative Oncology Group; ICH: International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use; MMR: mismatch repair; MSI: microsatellite instability; MSI-H: MSI-high; PCR: polymerase chain reaction; PD-L1: programmed death ligand-1; PS: performance status.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. Gastric Cancer. Version 1.2020 https://www.nccn.org/professionals/physician_gls/pdf/gastric_blocks.pdf.
Systemic Therapy for Unresectable Locally Advanced, Recurrent, or Metastatic Disease
(When Local Therapy Is Not Indicated)
Second-Line and Subsequent Therapy
Second-Line Therapy Category
Preferred
regimens
Ramucirumab + paclilaxel 1
Docetaxel 1
Paclitaxel 1
lrinotecan 1
Fluorouracil + irinotecan 2A
Pembrolizumab (MSI-H or dMMR tumors) 2A
Other
recommended
regimens
Ramucirumab 1
lrinotecan + cisplatin 2A
Entrectinib or larotrectinib (NTRK gene fusion–positive tumors) 2A
Docetaxel + irinotecan 2B
Useful in certain
circumstances
Fluorouracil + irinotecan + ramucirumab 2B
Third-Line Therapy Category
Preferred
regimens
Trifluridine + tipiracil 1
Pembrolizumab (MSI-H or dMMR tumors) 2A
Pembrolizumab (gastric adenocarcinoma with PD-L1 expression
levels by CPS ≥1)
2A

NCCN’s Principles of Pathologic
Review and Biomarker Testing1
PRACTICE AID
lmmunohistochemical Criteria for Scoring HER2 Expression in Gastric Cancer
Surgical Specimen
Expression Pattern,
lmmunohistochemistry
Biopsy Specimen
Expression Pattern,
lmmunohistochemistry
HER2 Overexpression
Assessment
0
No reactivity or membranous
reactivity in <10%
of cancer cells
No reactivity or no
membranous reactivity
in any cancer cell
Negative
1+
Faint or barely perceptible
membranous reactivity in
≥10% of cancer cells;
cells are reactive only in part
of their membrane
Cluster of five or more
cancer cells with a faint
or barely perceptible
irrespective of percentage
of cancer cells positive
Negative
2+
Weak to moderate complete,
basolateral, or lateral
in ≥10% of cancer cells
cancer cells with a weak
to moderate complete,
irrespective of percentage
Equivocal
3+
Strong complete,
in ≥10% of cancer cells
cancer cells with a strong
complete, basolateral,
or lateral membranous
reactivity irrespective
of percentage
Positive

PRACTICE AID
• Used for locally advanced, recurrent, or metastatic gastric cancer in patients who are
candidates for treatment with PD-1 inhibitors.
• Performed on formalin-fixed, paraffinembedded (FFPE) tissue
• Results interpreted as MSl-high (MSI-H) or mismatch repair-deficient (dMMR) in accordance
with CAP DNA Mismatch Repair Biomarker Reporting Guidelines
• Refer patients with MSI-H or dMMR tumors to a genetics counselor for further assessment
• No loss of nuclear expression of MMR proteins: no
evidence of deficient mismatch repair (low probability
of MSI-H)
• Loss of nuclear expression of one or more MMR
proteins: deficient mismatch repair
• Microsatellite stable (MSS)
• MSI-Low (MSI-L)
- 1%-29% of markers exhibit instability
- 1 of the 5 National Cancer Institute (NCI) or
mononucleotide markers exhibits instability
• MSI-High (MSI-H)
- ≥30% of the markers exhibit instability
- 2 or more of the 5 NCI or mono-nucleotide
markers exhibit instability
Microsatellite Instability (MSI) or Mismatch Repair (MMR) Testing
MMR
Interpretation
MSI
Interpretation

PRACTICE AID
CAP: College of American Pathologists; NCCN: National Comprehensive Cancer Network; PD-1: programmed cell death protein 1; PD-L1: programmed death-ligand 1.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. Gastric Cancer. Version 1.2020 https://www.nccn.org/professionals/physician_gls/pdf/gastric_blocks.pdf.
• Used for locally advanced, recurrent, or metastatic gastric carcinomas in patients who are
candidates for treatment with PD-1 inhibitors
• An FDA-approved companion diagnostic test for use on FFPE tissue is available as an aid
in identifying patients for treatment with PD-1 inhibitors
• Should be performed only in CLIA-approved laboratories
• This is a qualitative immuno-histochemical assay
using anti–PD-L1 antibodies for the detection of PD-L1
protein in FFPE tissues from gastric adenocarcinoma
• A minimum of 100 tumor cells must be present in the
PD-L1–stained slide for the specimen to be considered
adequate for PD-L1 evaluation
• A specimen is considered to have PD-L1 expression if
the Combined Positive Score (CPS) ≥1
- CPS is the number of PD-L1 staining cells
(ie, tumor cells, lymphocytes, macrophages)
divided by the total number of viable tumor cells,
multiplied by 100
PD-L1 Testing
Assessment
of PD-L1 Protein
Expression
in Gastric Cancers

Selected Clinical Trials in Gastric Cancer1
PRACTICE AID
Access the activity, “Up Close and Personalizing Gastric Cancer Care: Precision Medicine With HER2-Targeted Therapies
and Other Novel Agents,” at PeerView.com/JQB40
HER2+ Gastric Cancer
PD-1 Inhibitor + Monoclonal Antibody + CTX
NCT03615326: KEYNOTE-811
Recruiting 732 participants
Pembrolizumab + trastuzumab + CTX + placebo
ADC
NCT03329690: DESTINY-Gastric01
Active (220), not recruiting
Trastuzumab deruxtecan vs physician's choice (irinotecan or paclitaxel)
ADC + PD-1 Inhibitor
NCT04280341
Not yet recruiting (50)
RC48-ADC + JS001
Bispecific Antibody + CTX
NCT03929666
ZW25 vs physician's choice
ADC
NCT03556345
RC48-ADC
ADC
Trastuzumab deruxtecan
CTXorCTLA-4Inhibitor+PD-1Inhibitor+MonoclonalAntibody
NCT03409848: INTEGA
Ipilimumab or FOLFOX + nivolumab + trastuzumab
Monoclonal Antibody ± PD-1 Inhibitor ± CTX ± Dual CPI
NCT04082364: MAHOGANY
Margetuximab + INCMGA00012 + CTX + MGD013 + trastuzumab
Bispecific Antibody + PD-1 Inhibitor
+ CTX
NCT04276493
ZW25 + tislelizumab + CTX
Antiangiogenesis + CTX
NCT03081143: RAMIRIS
Ramucirumab + FOLFIRI
Monoclonal Antibody + PD-1 Inhibitor
NCT02689284
Margetuximab + pembrolizumab
ADC + PD-L1 Inhibitor + CTX
Trastuzumab deruxtecan vs trastuzumab
deruxtecan ± CTX ± durvaumab
Phase 3
Phase 2
Phase 1b/2
Phase 2/3
Phase 1

PRACTICE AID
Antiangiogenesis + PARP Inhibitor + Immunotherapy
(RiME)
NCT03995017
Ramucirumab + rucaparib ± nivolumab
PARP Inhibitor + Antiangiogenesis
NCT03008278
Olaparib + ramucirumab
Immunotherapy + Antiangiogenesis
+ CTX
NCT04069273: SEQUEL
Pembrolizumab + ramucirumab + paclitaxel
NCT02572687
Active, not recruiting (114)
Ramucirumab + durvalumab
+ CTX
NCT03966118
Avelumab + paclitaxel + ramucirumab
CTX + Antiangiogenesis
NCT03686488
trifluridine/tipiracil + ramucirumab
Phase 2
Phase 1
Phase 1/2
Antiangiogenesis Combinations

PRACTICE AID
Immunotherapy + CTX
NCT03745170: ORIENT-16
Sintilimab + CTX
Immunotherapy + CTX
NCT03675737:
KEYNOTE-859
Recruiting 1,542 participants
Pembrolizumab + CTX
Immunotherapy + CTX
NCT03221426:
KEYNOTE-585
Recruiting 1,000 participants
Pembrolizumab + CTX
Phase 3
Immunotherapy + PARP Inhibitor
NCT02734004: MEDIOLA
Durvalumab + olaparib + bevacizumab
Immunotherapy Combinations
NCT03281369
Atezolizumab + various combinations
PD-1 + CTLA-4 Inhibition
NCT04202601
Sintilimab + IBI310
Phase 1/2
Immunotherapy and Combinations
NCT03579784
Paclitaxel + olaparib then durvalumab
+ olaparib + paclitaxel
Immunotherapy + Monoclonal Antibody
NCT04099641
Bavituximab + pembrolizumab
Immunotherapy + DKK1 Neutralizing Antibody + CTX
NCT04363801: DisTinGuish
DKN-01 + tislelizumab ± CTX
NCT04209686
Paclitaxel + olaparib + pembrolizumab
Immunotherapy + TKI
NCT04164979
Cabozantinib + pembrolizumab
Phase 2
Phase 1
TKI + PD-L1 Inhibitor
NCT03539822: CAMILLA
Cabozantinib + durvalumab

PRACTICE AID
ADC: antibody–drug conjugates; CPI: checkpoint inhibitor; CTLA-4: cytotoxic T-lymphocyte–associated protein 4; CTX: chemotherapy; FGFR: fibroblast growth factor receptor; PARP: poly ADP-ribose polymerase; PD-1: programmed cell death protein 1; PD-L1: programmed
death-ligand 1.
1. https://clinicaltrials.gov.
PARP Inhibitor
NCT03427814: PARALLEL 303
BGB-290 vs placebo
Claudin 18.2-Positive
NCT03653507: GLOW
Zolbetuximab + CTX + placebo
FGFR Inhibitor
NCT03694522: FIGHT
Bemarituzumab + CTX + placebo
Claudin 18.2-Positive
NCT03504397: SPOTLIGHT
Zolbetuximab + CTX + placebo
CTX Platform Combo
NCT03368963
Trifluridine/tipiracil
+ nanoliposomal irinotecan
Phase 3
Phase 1/2
Other Therapies and Strategies
AKT Small Molecule Inhibitor
NCT01896531
Ipatasertib + CTX Claudin 18.2-positive
NCT03505320: ILUSTRO
Zolbetuximab + pembrolizumab + CTXFGFR Inhibitor
NCT04189445
Futibatinib
Phase 2

ASCO Guidance on Allocation of Scarce
Resources During COVID-19 Pandemic1,2
PRACTICE AID
What special training is necessary to prepare
my staff for a local outbreak of COVID-19?
Train staff on:
• Symptom recognition
• Screening procedures
• Use of Standard Precautions and personal protective
equipment (PPE)
• Obtaining SARS-COV2 testing for patients according to
current testing guidelines
• Protocols for triaging and assessing patients quickly
• Identifying and referring patients, families, and
coworkers to telephone-based mental health services
What patient scheduling changes should be made
while pandemic restrictions exist?
• Because of reduced waiting areas, the number of
appointments may have to be decreased or the time
between appointments may have to be increased
• Postpone routine follow-up visits of patients not
on active cancer treatment, including 6-month and
12-month survivorship visits
• Schedule brief, remote check-ins with patients on
maintenance therapies to ensure that they have
sufficient drug supplies; provide instructions on when
they should call their provider
• Institute direct telecommunication for survivorship
check-ins; create a timeline over the next months to
schedule calls
• Communicate COVID-19 information and the
rationale for changes in appointments via direct
telecommunication, websites, and patient portals
• Consider home collection of routine lab samples
instead of patient visits into the clinic; results can be
communicated via telephone
• For areas not yet affected by widespread, local
transmission, postpone nonurgent visits so urgent visits
can be scheduled more immediately
• Use telemedicine for patients not requiring a physical
exam, treatment, or in-office diagnostics
• Ask patients to use telephone triage, patient portals,
online assessment tools, or to call and speak with a staff
member
• Conduct remote check-ins to monitor high-risk
patients’ symptoms
What workplace changes should be made
to prepare for a local outbreak of COVID-19?
• If necessary, obtain additional PPE for staff members
who do not usually use it
• Limit facility access to one point of entry, if possible;
vendors, minimal ancillary services, most or all visitors,
and people younger than age 18 years should be
denied access
• Consider remote or virtual support services
• Establish outside triage stations with social distancing
of 6 feet apart to screen patients and visitors for
COVID-19 symptoms and fever before appointments
• Install barriers or social distancing mechanisms at front
desks if screening is not conducted outside of the
facility
• Convert waiting areas to allow for distancing of at least
6 feet (eg, move chairs, cordon off every other chair)
• Convert open infusion suites to semi-private spaces
with at least 6 feet distance between patients and/or
use available curtains as a barrier between patients
• Suspend (or move to a virtual platform) all onsite group
and patient activities (eg, yoga, education seminars,
support groups)
How should clinical trial investigators respond
to the COVID-19 pandemic?
• ASCO acknowledges that conducting clinical trials will
be particularly challenging during this time
• The FDA has issued guidance on management of
clinical trial patients during the coronavirus pandemic
– Go to: https://www.fda.gov/regulatory-information/
search-fda-guidance-documents/fda-guidance-
conduct-clinical-trials-medical-products-during-
covid-19-public-health-emergency
• The National Cancer Institute has issued guidance on
the NCI Central Institutional Review Board
– https://www.cancer.gov/research/key-initiatives/
covid-19
• For more guidance and information on COVID-19
and HCC management, visit
– https://www.asco.org/asco-coronavirus-information
– https://ilca-online.org/management-of-hcc-during-
covid-19-ilca-guidance/

ASCO: American Society of Clinical Oncology; HCC: hepatocellular carcinoma.
1. https://www.sirweb.org/practice-resources/toolkits/covid-19-toolkit/covid-19-planning. 2. https://www.asco.org/asco-coronavirus-information/provider-practice-preparedness-covid-19.
ASCO Guidance on Allocation of Scarce
Resources During COVID-19 Pandemic1,2
PRACTICE AID
What screening and infection prevention and control practices should my workplace undertake?
• To address asymptomatic or presymptomatic transmission, everyone should put on a face mask or other face
covering—regardless of symptoms—before entering the facility
• When scheduling appointments, ask patients to call ahead and discuss the need to reschedule their appointments if
they develop symptoms of a respiratory infection (eg, cough, sore throat, fever) on the day they are scheduled to be seen
• Contact the patient the day before the appointment and screen for symptoms of cough, sore throat, fever, or other
flu-like symptoms
– If symptoms are present, use triage protocols to determine if an appointment is necessary or if the patient can be
managed from home
– If the patient can be managed from home, the patient should be rescheduled until such time when he or she is
determined to be no longer infectious
What screening and infection prevention and control practices should my workplace
undertake upon patient arrival or during the visit?
• Allow only essential visitors who are not displaying symptoms of a respiratory or other infection; if essential, limit the
number to one visitor per patient for all provider visits
• Visitors should not enter communal treatment areas—ask them to wait in vehicles or return after treatment
• Encourage use of alternative mechanisms for patient and visitor interactions, such as video-calls on cell phones or
tablets
• Healthcare personnel should wear facemasks at all times while they are in the healthcare facility; when available,
facemasks are preferred over cloth face coverings, because they protect the wearer from exposure to infectious
material from others
• Healthcare personnel screening patients and visitors at arrival should wear PPE (including masks) and have access to
waste bins and cleaning/disinfecting agents
• Ask patients and visitors if they have symptoms of cough, sore throat, or fever; if they’ve been out of the country in the
past 14 days; or if they’ve been exposed to anyone with respiratory symptoms or known COVID-19; when available,
use an infrared thermometer to take temperatures during screening
• Provide signage with COVID-19 screening questions and visualization of symptoms for all patient/visitors, as well as
patient education materials and illustrations of proper hygiene for infection prevention and symptoms to report
• Patients with suspected infection should receive a facemask and be rapidly isolated until more thorough screening or
testing can be conducted. Isolation should take place in an exam room or other private area with the door closed
• All staff entering the room of a patient with known or suspected COVID-19 should adhere to Standard Precautions
and use a N95 respirator or facemask, gown, gloves, and eye protection; cloth face coverings are not proven effective
PPE and should not be worn for the care of patients with known or suspected COVID-19 or other situations where a
respirator or facemask is warranted
• Establish a plan of action for patients who present with respiratory symptoms (eg, resource for testing, schedule patient
with primary care or local/health department)

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Up Close and Personalizing Gastric Cancer Care: Precision Medicine With HER2-Targeted Therapies and Other Novel Agents