Candid Conversations on Modern Urothelial Cancer Management: Personalizing Patient Care Using the Latest Evidence and Innovative Therapeutic Strategies

Chair and Presenters, Andrea Necchi, MD, Matthew D. Galsky, MD, Shilpa Gupta, MD, and Michiel S. van der Heijden, MD, PhD, prepared useful Practice Aids pertaining to bladder cancer for this CME/MOC/NCPD/AAPA/IPCE activity titled “Candid Conversations on Modern Urothelial Cancer Management: Personalizing Patient Care Using the Latest Evidence and Innovative Therapeutic Strategies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/4cDsBog. CME/MOC/NCPD/AAPA/IPCE credit will be available until June 30, 2025.

1. Adverse Event Management Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/GJT40 Educating Patients About ADCs
1-3
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
•May be improved/resolved with a
treatment hold
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

2. Adverse Event Management Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/GJT40 FGFR Alterations Are Frequently Observed in Bladder Cancer
4,5
Erdafinitib: Understanding Safety Considerations
6,7
 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)
 All members of the care team have
important roles in educating patients on
the implications of genomic testing
Eligibility for FGFR inhibition requires
testing for genomic alterations 
•FGFR3 inhibitors are associated with
unique AEs
•Oral hygiene is 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

3. Adverse Event Management Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/GJT40
1. Hanna KS et al. Am J Health-Syst Pharm. 2022;79:629-635. 2. Trodelvy (sacituzumab govitecan-hziy) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761115s035lbl.pdf. 3. Padcev (enfortumab vedotin) Prescribing Information.  
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761137s024s025lbl.pdf. 4. Knowles MA et al. Nat Rev Cancer. 2015;15:25-41. 5. Nimgaonkar N et al. JAMA Oncol. 2022;8:1070-1072. 6. Loriot Y et al. N Engl J Med. 2019;381:338-348. 7. Siefker-Radtke AO et al. Lancet Oncol. 
2022;23:248-258. 8. Martins F et al. Nat Rev Clin Oncol. 2019;16:563. 9. Postow MA et al. N Engl J Med. 2018;378:158-168. 10. Schneider BJ et al. J Clin Oncol. 2021;39:4073-4126. 11. NCCN Clinical Practice Guidelines in Oncology. Management of Immunotherapy-Related Toxicities. 
Version 1.2024. https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Counseling Patients on irAEs Associated With Immune Checkpoint Inhibitors
8-11
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 o f Treatment, wk
0 4 6 8 10 12 14 >30
Toxicity, Grade
Colitis
Endoc rinopa thy
Nephritis
Liver toxicity
Skin toxicity,
rash, or
pruritus
Pneumonitis

4. Expanding Role of Therapeutic Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/GJT40
Approaches for MIBC
1
Nivolumab
FDA approved for the adjuvant treatment of patients with MIBC who are at high risk of recurrence after
undergoing radical resection (phase 3 CheckMate -274)
Pembrolizumab
Met DFS primary endpoint for adjuvant treatment of patients with MIBC (phase 3 AMBASSADOR 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 Setting
•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; under FDA Priority
Review
•Phase 3 EV-302/KEYNOTE A-39:
enfortumab vedotin + pembrolizumab vs
chemo; FDA approved
Second-Line Setting
•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; FDA approved
•Phase 3 TROPiCS-04: sacituzumab
govitecan vs chemo
Approaches for Unresectable or mUC
1

5. Expanding Role of Therapeutic Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/GJT40
Understanding the Impact of Subcutaneous Immune Checkpoint Inhibitors
2,3
SC Administration Provides an Alternative With Benefits for Both Patients and Providers
Immune Checkpoint Inhibitors Are Approved Across Many Tumor Types
• IV infusions can be associated with treatment burdens (eg, long
administration times, risk for complications)
• SC approaches will have an impact not only for the patient but also for
healthcare professionals, as it will affect the organization of care
Patient
convenience
Administration
time
Level of
invasiveness
Infusion
center
availability
PATIENT
• Alleviates need for
IV vein ports
• Allows for more
flexibility/reduced
treatment burden
• Reduces loss of
work productivity
• Provides improved
perceived quality of life
CARE TEAM
• Reduces dose
preparation and
administration times
• Optimizes occupancy
in infusion centers
• Improves healthcare
resource utilization
• Reduces
administrative
burden
BOTH
• Supports more
convenient
administration
locations (remote
areas or smaller
healthcare settings)
• Decreases
administration time
• Allows for streamlined
process

How Can We Improve the Patient Experience?

6. Expanding Role of Therapeutic Approaches in Bladder Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/GJT40
1. clinicaltrials.gov. 2. Lonardi S et al. ESMO 2022. Abstract 739P. 3. https://dailynews.ascopubs.org/do/subcutaneous-immune-checkpoint-inhibitors-friends-foes. 4. Balar AV et al. Lancet Oncol. 2021;22:919 -930.
Select Clinical Trials for NMIBC
1
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 trial
2
Clinical Trials Testing Intravesical Approaches
• Phase 2 SunRISe-1: TAR-200 in BCG-unresponsive NMIBC
• Phase 2 SunRISe-3: TAR-200 in BCG-naïve NMIBC
• Phase 3 SunRISe-5: TAR-200 vs intravesical chemo in
BCG-unresponsive NMIBC
• Phase 1 EV 104: EV in BCG-unresponsive NMIBC
• Phase 1 TAR-210: high-risk or intermediate-risk NMIBC with FGFR alterations
• Phase 3 MoonRISe-1: TAR-210 vs IV chemo in intermediate-risk NMIBC
with 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 +
immune checkpoint
inhibitor
BCG induction only +
immune checkpoint
inhibitor
BCG induction +
maintenance
R

7. Patient Resources
for Healthcare Professionals
1

Full abbreviations, accreditation, and disclosure information available at
PeerView.com/GJT40
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.
Get Yours Today!
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 (English & Spanish editions)
• Patient videos
• Webinars
• Podcasts
• Treatment matrix
• Clinical trials dashboard
• Bladder cancer support line: 833-ASK-4-BCA