A 76-year-old man presented to the clinic with complaints of dizziness and hematuria.
PMH: hypercholesterolemia (well controlled with medication) and mild COPD.
SH: Patient does not smoke or drink alcohol.

Initial Clinical Workup:

CT Imaging: 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)
Lung Biopsy confirmed stage IV urothelial carcinoma.
Molecular testing: FGFR2/3 mutation and fusion negative

Treatment and Disease Progression:

Patient is initiated with neoadjuvant gemcitabine plus cisplatin for 4 cycles.
- He achieved a partial response following chemotherapy.
- Following neoadjuvant therapy, the patient undergoes surgical resection of the tumor.
- While discussed with his oncology care team, the patient did not receive maintenance treatment.
6 months following surgery, patient demonstrates disease progression based after routine follow up and repeat imaging.
- Patient progresses to muscle-invasive metastatic urothelial carcinoma.
- Patient is started on combination pembrolizumab plus enfortumab vedotin-ejfv.
  - Pembrolizumab 200 mg IV every 3 weeks; enfortumab 1.25 mg/kg IV infusion over 30 minutes on Days 1 and 8 for every 21-day cycle.
  - 12 hours post-infusion, the patient developed a maculopapular rash and was improved with supportive care (topical hydrocortisone cream).
- Achieves partial response after 6 cycles.
Following initial systemic therapy, patient is evaluated in a routine follow up visit and demonstrates further disease progression.
- After discussion with his oncology care team, the patient is initiated on sacituzumab govitecan 10 mg/kg IV on D1 and D8 for 21-day cycles.
  - 48 hours following start of therapy, patient notices feeling dehydrated and having more frequent bowel movements. His oncologist starts him on oral loperamide to manage his diarrhea. Two days later, the patient’s diarrhea was resolved.

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 presented a case of a 76-year-old male with metastatic urothelial carcinoma involving the bladder and multiple liver metastases. His kidney function was impaired with an estimated glomerular filtration rate (eGFR) of 45 mL/min, making him ineligible for cisplatin chemotherapy. Molecular testing was negative for FGFR alterations.

With metastatic disease and good performance status but cisplatin-ineligibility, combination immunotherapy was recommended over single agent chemotherapy. Dr. Tagawa noted that the combination of enfortumab vedotin (an antibody-drug conjugate targeting Nectin-4) plus pembrolizumab is given on a 3-week cycle, with enfortumab vedotin dosed on days 1 and 8 and pembrolizumab at 200 mg flat dose every 3 weeks.

This patient developed a maculopapular rash after starting therapy that improved with topical steroids. He achieved a partial response after 6 cycles but then had persistent grade 2 neuropathy requiring enfortumab vedotin discontinuation. Pembrolizumab was continued as maintenance, but he eventually had disease progression.

Next treatment was sacituzumab govitecan on day 1 and day 8 of a 21-day cycle, typically at 10 mg/kg. Dr. Tagawa again reviewed that key adverse events with this Trop-2 antibody-drug conjugate are neutropenia and diarrhea, requiring monitoring and potential dose modifications.

In conclusion, Dr. Tagawa walked through treatment decision-making in a cisplatin-ineligible patient with advanced urothelial carcinoma. The case highlighted evolving use of immunotherapy combinations and newer antibody-drug conjugates for patients progressing after first-line immunotherapy. Molecular profiling for biomarker-driven therapy eligibility should be incorporated at diagnosis and upon progression.

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