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 key adverse events associated with sacituzumab govitecan (Trodelvy) in metastatic urothelial carcinoma. The main toxicities are neutropenia and diarrhea.

Overall, about one third of patients experience grade 3-4 neutropenia. Febrile neutropenia, which requires prompt evaluation and treatment, occurs in approximately 10% of patients per trial data. Dr. Tagawa noted that many urothelial carcinoma patients have risk factors predisposing to neutropenia based on ASCO guidelines. Strategies to mitigate neutropenia risk include dose delays/reductions and growth factor support. Through these interventions, most patients can continue sacituzumab govitecan with adjusted dosing.

The other common toxicity is diarrhea, which affects over 50% of patients. However, grade 3 diarrhea occurred in about 10% of patients in trials. Grade 2 diarrhea, defined as up to 7 loose stools above baseline per day, is also clinically meaningful. Dr. Tagawa emphasized patient education on diarrhea risk and preemptive use of antidiarrheals starting with cycle 1. Diarrhea onset is typically acute following infusion. While some dose reductions are needed for persistent higher grade diarrhea, most cases can be managed supportively.

In summary, Dr. Tagawa reviewed key toxicity monitoring and management approaches for patients receiving sacituzumab govitecan for advanced urothelial carcinoma. As a newer therapy, vigilance for neutropenia and diarrhea is imperative, given potential to cause serious complications. Through dose modifications and supportive care interventions, majority of patients can continue treatment safely. Ongoing research is investigating biomarkers or clinical factors associated with increased toxicity risk on sacituzumab govitecan.

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