A 72-year-old man presented to the clinic with complaints of dizziness and hematuria.
PMH: Obesity (BMI) and poorly controlled type 2 diabetes (blood sugar, 200 mg/dL)
SH: Patient does not smoke and occasionally drinks, in social settings.

Initial Clinical Workup:

CT of chest, abdomen, and pelvis revealed a 3.5-cm mass in the bladder and multiple liver metastases
ECOG PS 1
eGFR > 60 mL/min (cisplatin-eligible kidney function)
Biopsy/pathology confirmed stage IV metastatic urothelial carcinoma
Molecular testing: FGFR2/3 mutation and fusionnegative

Initial Treatment and Disease Progression:

Patient received platinum-based chemotherapy with cisplatin.
- Experiences platinum-based peripheral neuropathy (paresthesia) that interrupted the patient’s quality of life.
  - Neuropathy was low grade AE (Grade 1)which improved to Grade 0 with supportive care.
- Partial response after 4 cycles of cisplatin; ECOG PS 1
- Imaging showed no growth of existing lesions or new lesions after 4 cycles 
Followed with IO maintenance with avelumab 800 mg IV infusion over 60 minutes every two weeks.
- Following 9 cycles, patient achieved partial response in the lung and bladder.
- Liver function tests, CrCl, and other labs were within normal limits
- No infusion reactions
- 5 months later, disease progression is confirmed
Patient was initiated on sacituzumab govitecan 10 mg/kg on Days 1 and 28 for 21-day continuous treatment cycle.
- Patient experiences grade 3 neutropenia at the time of schedule treatment.
- Delay dosing by 2 weeks until recovery to less than grade 1. Managed with 25% dose reduction and administration of G-CSF.

This is a synopsis of a Case-Based Peer Perspectives series featuring Scott T. Tagawa, MD, MS, FACP, FASCO, of Weill Cornell Medicine.

Scott T. Tagawa, MD, MS, FACP, FASCO discussed new data supporting use of targeted therapies after progression on first-line platinum chemotherapy and immune checkpoint inhibition in advanced urothelial carcinoma.

He first mentioned erdafitinib, a pan-FGFR inhibitor. Data presented at ASCO 2023 showed improved outcomes with erdafitinib versus chemotherapy in patients with FGFR3 mutations or FGFR2/3 fusions. As FGFR alterations are found in 15-20% of urothelial carcinomas, Dr. Tagawa emphasized checking for these biomarkers in all patients.

He then discussed results of the phase 3 EV-301 trial leading to FDA approval of enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, for locally advanced or metastatic urothelial carcinoma after platinum chemotherapy and checkpoint inhibition. Enfortumab vedotin improved overall survival, progression-free survival, and response rate versus chemotherapy. However, there are unique adverse events, including ocular toxicity and fatal hyperglycemia, requiring monitoring and dose modifications.

Dr. Tagawa next reviewed data on sacituzumab govitecan, an antibody-drug conjugate linking SN-38 (active metabolite of irinotecan) to an anti-Trop-2 antibody. Results from the phase 2 TROPHY-U-01 trial in ≥3rd line metastatic urothelial carcinoma showed an overall response rate of 27-29%. This led to accelerated FDA approval given response rate improvements over historical chemotherapy.

In conclusion, Dr. Tagawa summarized emerging data supporting new targeted therapies in specific molecularly-defined subsets of metastatic urothelial carcinoma. Biomarker analysis at diagnosis is key to identify patients who may benefit. Research continues with additional targeted agents and immunotherapies aiming to improve outcomes in advanced disease.

*Video synopsis is AI-generated and reviewed by Urology Times editorial staff.