Chair and Presenter Neal D. Shore, MD, FACS, Sia Daneshmand, MD, and Guru P. Sonpavde, MD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC/AAPA activity titled “Pioneering Precision Medicine in Bladder Cancer: Multidisciplinary Perspectives on Personalizing Patient Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/40qGkJH. CME/MOC/AAPA credit will be available until December 28, 2024.

1. Treatments Used in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/XJV40
Counseling Patients on irAEs Associated With Immune Checkpoint Inhibitors1-4
Patient education must focus
on the importance of prompt
recognition and management
of irAEs
Grade 1
Minimal or no symptoms; diagnostic change only
• In general, immune checkpoint inhibitor therapy should be continued with
close monitoring, with the exception of some neurologic, hematologic, and
cardiac toxicities
Grade 2
Mild to moderate symptoms
• Hold checkpoint inhibitor therapy for most grade 2 toxicities
• Consider resuming immunotherapy when symptoms and/or laboratory
values revert to grade 1 or lower
• Corticosteroids (initial dose of 0.1-1 mg/kg/d of prednisone or equivalent)
may be administered
Grade 3/4
Severe or life-threatening symptoms
Grade 3
• Hold checkpoint inhibitor therapy
• Initiate high-dose corticosteroids (prednisone 1-2 mg/kg/d or
methylprednisolone IV 1-2 mg/kg/d)
• If symptoms do not improve with 48-72 h of high-dose corticosteroids,
infliximab may be offered for some toxicities
• Taper corticosteroids over the course of at least 4-6 wk
• When symptoms and/or laboratory values revert to grade 1 or lower,
rechallenging with immunotherapy may be offered; however, caution is
advised, especially in those patients with early-onset irAEs; dose
adjustments are not recommended
Grade 4
• In general, permanent discontinuation of checkpoint inhibitor therapy is
warranted, with the exception of endocrinopathies that have been
controlled by hormone replacement
irAE Grading and Management: Overall
• Diarrhea
• Nausea/Vomiting
• Hepatitis
Gastrointestinal
• Hypothyroidism
Endocrine
• Rash
• Pruritus
Dermatologic
• Pneumonitis
Pulmonary
irAEs Can Affect Any Organ System …
… And the Timing of Events Is Variable
Duration of Treatment, wk
0 4 6 8 10 12 14 >30
Toxicity,
Grade
Colitis
Endocrinopathy
Nephritis
Liver toxicity
Skin,
rash, or
pruritus
Pneumonitis

2. Treatments Used in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/XJV40
Educating Patients About ADCs5-7
Enfortumab
Vedotin (EV)
Sacituzumab
Govitecan (SG)
Dosing
Schedule
2 doses in a
21-d cycle
Infusion
Time
Administered over 3 h
for the first dose,
with subsequent doses
administered over 1-2 h
Dose
Rounding
Administered
over 30 min
3 doses in a 28-d cycle
as monotherapy
2 doses in a 21-d cycle
in combination with
pembrolizumab
Available as 20-mg and
30-mg vials, allowing
flexibility with dose
rounding
Available as a
180-mg vial
 Assess patients with a thorough
history and physical examination
 Screen for pre-existing neuropathy
or diabetes mellitus
Before a patient starts
treatment with either
EV or SG …
• There is a risk of infusion-related reactions
• Although rare, grade 3-4 reactions do occur
– Infusion-site extravasation observed with
EV; ensure adequate venous access
prior to infusion
• Hypersensitivity reactions, ranging from mild
to anaphylaxis, have been seen within 24 h
of SG administration
– Premedicate with an antipyretic and H1
and H2 blockers prior to each infusion
– Have medication and emergency
equipment to treat such reactions ready
for immediate use
• Monitor patients during the infusion and for
≥30 min after completion of infusion
Safety Considerations With ADCs
Peripheral Neuropathy
• Generally resolves/remains at grade 1
Hyperglycemia
• Monitor blood glucose in patients with/at
risk for diabetes or hyperglycemia
Ocular Disorders
• Monitor and consider prophylactic
artificial tears for dry eyes and treatment
with ophthalmic topical steroids after an
ophthalmic examination
Neutropenia
• Consider growth factor support
• Dose reduction/hold
Diarrhea
• Educate patients
• Maintain hydration with electrolytes
• Antidiarrheal medications/best
supportive care
Management Strategies for Common AEs
EV SG

3. Treatments Used in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/XJV40
1. Martins F et al. Nat Rev Clin Oncol. 2019;16:563. 2. Postow MA et al. N Engl J Med. 2018;378:158-168. 3. Schneider BJ et al. J Clin Oncol. 2021;39:4073-4126. 4. NCCN Clinical Practice Guidelines in Oncology. Management of Immunotherapy-Related Toxicities. Version 3.2023. https://www.nccn.org/
professionals/physician_gls/pdf/immunotherapy.pdf. 5. Hanna KS et al. Am J Health-Syst Pharm. 2022;79:629-635. 6. Trodelvy (sacituzumab govitecan-hziy) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761115s035lbl.pdf. 7. Padcev (enfortumab vedotin)
Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761137s020lbl.pdf. 8. Knowles MA et al. Nat Rev Cancer. 2015;15:25-41. 9. Nimgaonkar N et al. JAMA Oncol. 2022;8:1070-1072. 10. LoriotY et al. N Engl J Med. 2019;381:338-348. 11. Siefker-Radtke AO et al.
Lancet Oncol. 2022;23:248-258.
FGFR Mutations Are Frequently Observed in Bladder Cancer8,9
Erdafinitib: Understanding Safety Considerations10-11
 Patients ideally undergo testing upon
diagnosis
 Options include specifically testing tumors
for FGFR3 alterations (eg, RT-PCR
companion assay) or more comprehensive
approaches (eg, NGS panels, liquid biopsy)
 Both nurses and oncologists have
important roles in educating patients on
the importance of genomic testing
Eligibility for FGFR inhibition requires
testing for genomic alterations
• FGFR3 inhibitors are associated with
unique AEs
• Oral hygiene critical; mucositis and
other oral toxicities can be a concern
• Monitor for skin and nail toxicities,
referring to dermatology and podiatry
as needed
• Close monitoring and supportive care is
important
General Guidance on AEs
Associated With FGFR3 Inhibitors • Erdafitinib also inhibits FGFR signaling
in the proximal renal tubule, impairing
function of the sodium-dependent
phosphate co-transporter
• Dietary phosphate may require
restriction
– Consult a nutrition professional
(eg, registered dietitian, nutritionist)
for individualized dietary planning
– Consider adding a non–calcium-
containing phosphate binder (eg,
sevelamer carbonate)
• Recommended ophthalmologic
examinations
– Monthly for first 4 mo; every 3 mo
thereafter
– At any time for visual symptoms
• For any occurrence of central serous
retinopathy (CSR)/retinal pigment
epithelial detachment (RPED):
– Withhold erdafitinib; discontinue
permanently if symptoms do not
resolve in 4 wk
– Discontinue permanently for
grade 4 CSR/RPED
Bladder
lumen
Lamina
propria
Inner
muscle
Outer
muscle
Tis Ta
T1
T2a T2b T3
T4
Tumor invades
adjacent tissues
and organs
Tumor invades
perivesical tissue
Tumor invades
deep muscle
Tumor invades
superficial muscle
Tumor invades
subepithelial
connective tissue
Noninvasive
papillary
carcinoma
Carcinoma
in situ
Urothelium
Non-Muscle Invasive Muscle Invasive Metastatic
>60% ~30% ~30% ~20%
Hyperphosphatemia Ocular Toxicities

4. Expanding Role of Therapeutic Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/XJV40
Neoadjuvant immunotherapy is administered before surgery and can reduce the
size of the primary tumor as well as eliminate residual cancer cells left after surgery
Rationale
• Lower disease burden and intact
immune system
• T-cell response generated against
in situ primary tumor with diverse
antigen load
• Fast endpoints to assess response
• Allows for translational research:
biologic and immunologic
correlative studies
Rationale
• Immunologic pathways are
disrupted by surgical stress
• No risk for delaying surgery with
adjuvant versus neoadjuvant
approach
• Prior chemotherapy or other
systemic/local therapies may help
augment immune responses
Adjuvant immunotherapy is administered after surgery and leads to an increase
in activated T cells that can eliminate residual cancer cells in the tumor bed
Comparison of Neoadjuvant and Adjuvant Treatment Approaches1
Immunotherapy
T cells
T-cell activation Resection surgery
Solid tumor Resection surgery Immunotherapy T-cell activation
and additional
immunotherapy
Tumor cells Artery Healthy cells Immunotherapy

5. Expanding Role of Therapeutic Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/XJV40
Select Clinical Trials for NMIBC3
Pembrolizumab
FDA approved for the treatment of patients with BCG-unresponsive, high-risk NMIBC with carcinoma in situ with or without
papillary tumors who are ineligible for or have elected not to undergo cystectomy based on the KEYNOTE-057 trial2
Clinical Trials Testing TAR-200
• Phase 2 SunRISe-1: TAR-200 in BCG-unresponsive
• Phase 2 SunRISe-3: TAR-200 in BCG-naive
• Phase 1 TAR-210: FGFR alterations
Intravesical drug delivery system that enables a
sustained release of gemcitabine (TAR-200) or
erdafitinib (TAR-210) into the bladder, increasing the
dwell time of the local drug concentration
TAR-200/TAR-210
Clinical Trials Testing BCG + IO
• Phase 3 POTOMAC: BCG + durvalumab
• Phase 3 KEYNOTE-676: BCG + pembrolizumab
Key Eligibility Criteria
• High-risk NMIBC
• No prior BCG therapy
BCG
induction/maintenance +
CPI
BCG induction only +
CPI
BCG induction +
maintenance
R

6. Expanding Role of Therapeutic Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/XJV40
1. Versluis JKM et al. Nat Med. 2020;26:475-484. 2. Balar AV et al. Lancet Oncol. 2021;22:919-930. 3. clinicaltrials.gov.
Approaches for MIBC3
Nivolumab
FDA approved for the adjuvant treatment of patients with MIBC
who are at high risk of recurrence after undergoing radical
resection based on the CheckMate -274 trial
Cisplatin-Eligible Trials
• Phase 3 ENERGIZE: gem/cis ±
nivolumab (fully accrued N = 861)
• Phase 3 NIAGARA: gem/cis ±
durvalumab (fully accrued N = 1,063)
• Phase 3 KEYNOTE-866:
gem/cis + pembrolizumab
(fully accrued N = 907)
• Phase 3 KEYNOTE-B15/EV-304:
pembrolizumab + EV
Cisplatin-Ineligable Trials
• Phase 3 KEYNOTE-905/EV-303:
pembrolizumab + EV
• Phase 3 VOLGA: durvalumab +
tremelimumab + EV
• Phase 2 SunRISe-4: TAR-200 +
cetrelimab
R
Cisplatin Ineligible
Neoadjuvant Phase
1:1:1
IO
IO +
novel agent
Radical cystectomy and
pelvic lymph node dissection
Adjuvant Phase
IO
IO +
novel agent
Observation
R
Cisplatin Eligible
Radical cystectomy and
pelvic lymph node dissection
Neoadjuvant Phase Adjuvant Phase
IO + chemo or
IO + novel agent
Placebo + chemo
IO or IO +
novel agent
Placebo
1:1
First-Line:
• Phase 2 BAYOU: durvalumab ± olaparib
in platinum-ineligible patients
• Phase 3 NILE: durvalumab + chemo ±
tremelimumab vs chemo
• Phase 3 CheckMate -901: nivolumab +
gem/cis vs gem/cis
• Phase 3 EV-302/KEYNOTE A-39:
enfortumab vedotin + pembrolizumab vs
chemo
Second-Line:
• Phase 2 DS8201-A-U105: T-DXd +
nivolumab
• Phase 2 DESTINY PanTumor02: T-DXd
in HER2+ mUC
• Phase 2 NORSE: erdafitinib + cetrelimab
vs erdafitinib
• Phase 3 THOR: erdafitinib vs chemo vs
pembrolizumab in patients with selected
FGFR mutations
• Phase 3 TROPiCS-04: sacituzumab
govitecan vs chemo
Approaches for Unresectable or mUC3

7. Patient Resources
for Healthcare Professionals1
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/XJV40
1. https://bcan.org.
The Bladder Cancer Advocacy Network (BCAN) is a national
advocacy organization that is committed to advancing bladder
cancer research and supporting those impacted by the disease.
BCAN provides free online and printed
educational resources designed to help
patients, caregivers, and the medical
community learn about bladder cancer
and treatment options.
• Printed materials
• Patient videos
• Webinars
• Podcasts
• Treatment matrix
• Clinical trials dashboard
• Bladder cancer support line:
833-ASK-4-BCA
Get Yours Today!