Frontline Options for Metastatic Urothelial Cancer: Tailoring Treatment Choices


Diverse approaches to frontline treatment for metastatic urothelial cancer, including eligibility for cisplatin-based chemotherapy, alternative regimens, and the impact of drug shortages on treatment decisions.


Arlene O. Siefker-Radtke, MD: We currently have multiple approaches to the frontline treatment of our metastatic urothelial cancer patients. At the moment, it’s mostly divided based on how eligible they are for a cisplatin-based chemotherapy regimen. Patients with initial metastatic disease who are cisplatin eligible really should receive a cisplatin-based chemotherapy. We currently have the standard of maintenance therapy for any patient with stable disease or better following their frontline treatment for metastatic urothelial carcinoma. And I think that is the most common approach that I’m seeing and should be discussed with our patients.

Unfortunately, we are treating a geriatric, elderly, frail patient population, often with comorbid medical conditions. And it’s estimated in some series that over 50% of patients are not eligible for standard-of-care cisplatin-based chemotherapy. This may be due to a GFR [glomerular filtration rate] less than 60 ml per minute or grade 2 peripheral neuropathy or grade 2 hearing loss. A class 3 congestive heart failure is another reason patients may not be eligible for standard-of-care cisplatin. In that setting, patients most commonly have received gemcitabine-carboplatin based on early clinical activity and an improved toxicity profile compared to the M-CAVI regimen of methotrexate, carboplatin, vinblastine.

And again, patients who receive gemcitabine-carboplatin and have stable disease are better can be offered maintenance avelumab in the maintenance phase to help extend or delay progressive disease. Maintenance avelumab also improved overall survival compared to best supportive care. However, we have been seeing challenges recently with our ability to obtain access to drugs, access to agents like cisplatin and carboplatin. And I know the cisplatin and carboplatin shortage has impacted academic centers across the US and I’ve heard even from our colleagues on the frontlines and the community, [it] has had a major impact on you as well.

One option that we’ve had recently approved with FDA-accelerated approval is in enfortumab vedotin plus pembrolizumab. This combination has been granted accelerated approval for patients with metastatic disease who are cisplatin ineligible in the frontline setting. So it’s wonderful to have an alternative while these shortages are going on. When we look at enfortumab vedotin with pembrolizumab in the frontline setting, we see objective response rates of around 64% and a median survival that was recently reported in the Journal of Clinical Oncology of around 22 months. So it does look like EV-pembro, or enfortumab vedotin plus pembrolizumab, may be an attractive option for the frontline treatment of metastatic urothelial cancer patients.

Transcript is AI-generated and edited for clarity and readability.

Case: A 73-Year-Old Man with Metastatic Urothelial Carcinoma

Initial Clinical Presentation:

  • A 73-year-old man presented to you from their local urologist with dizziness and hematuria
  • PMH: hypertension and diabetes (uncontrolled)
  • SH: former smoker; consumes alcohol 2-3 times per week
  • Chest x-ray and CT revealed a 3.7-cm mass on the right lateral wall of the bladder and liver metastases
  • Cystoscopic biopsy/pathology confirmed stage IV urothelial carcinoma
  • ECOG PS 1
  • CrCl 65 mL/min
  • The patient received gemcitabine + cisplatin (6 cycles)
    • Partial response at completion of chemotherapy
    • No maintenance therapy given, although discussed with patient

Current Clinical Presentation:

  • 7 months later, disease progression was discovered on routine follow up imaging


  • The patient received pembrolizumab and a partial response was achieved at 6 cycles
  • Molecular testing showed no FGFR2 mutation or fusion
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