Initial systemic therapy for metastatic urothelial carcinoma

ECOG: Eastern Cooperative Oncology Group; MVAC: methotrexate, vinblastine, doxorubicin, and cisplatin; NYHA: New York Heart Association.

* Creatinine clearance <60 mL/min is not a contraindication to cisplatin chemotherapy if kidney function is due to tumor obstruction and can be reversed.

¶ Enfortumab vedotin is typically administered in combination with pembrolizumab for a median of 7 to 9 cycles, if tolerable, mainly to avoid the risk of cumulative neurotoxicity. Pembrolizumab is then continued as monotherapy for up to 24 months or until disease progression or unacceptable toxicity during that period.

Δ Either option is appropriate, as the optimal sequencing of chemotherapy and immunotherapy (concurrent versus sequential) is not established.

◊ Nivolumab is administered in combination with gemcitabine and cisplatin every 3 weeks for up to 6 cycles. Nivolumab is then continued as monotherapy for up to 24 months or until disease progression or unacceptable toxicity during that period.

§ The choice between available cisplatin-based regimens is individualized based on patient and provider preferences.

¥ For patients without disease progression on platinum-based chemotherapy regimens, we offer maintenance avelumab. Patients without disease progression who are not eligible for maintenance immunotherapy may be observed with best supportive care.

‡ Patients who are candidates for combination therapy may have appropriate performance status but otherwise be ineligible for cisplatin-based combination chemotherapy due to kidney dysfunction, neuropathy, severe hearing loss, or heart failure.