Treatment of Metastatic Urothelial Carcinoma When Enfortumab Vedotin Is Contraindicated or Unavailable
Clinical Scenario
This protocol covers patients with metastatic or unresectable urothelial carcinoma who are fit (ECOG performance status 0–1) and have a glomerular filtration rate above 50 mL/min, qualifying them for cisplatin-based chemotherapy — but who have contraindications to enfortumab vedotin or for whom enfortumab vedotin is not available.
Reasons a patient may not be eligible for enfortumab vedotin include uncontrolled diabetes, peripheral neuropathy (grade 2 or higher), or pre-existing significant skin disorders.
Treatment Approach
For these cisplatin-eligible patients, the approach involves platinum-based combination chemotherapy combined with checkpoint inhibitor immunotherapy, followed by a maintenance immunotherapy phase in appropriate responders — though the specific regimen options, sequencing, and duration criteria are set out in the full protocol.
References
If contraindications for EV (or EV not available) and cisplatin-eligible: Offer cisplatin/gemcitabine in combination with CPI nivolumab.
If contraindications for EV or EV not available: Offer platinum-containing combination chemotherapy (cisplatin or carboplatin plus gemcitabine) followed by maintenance treatment with CPI avelumab in patients with at least stable disease on chemotherapy.
Some patients might not be eligible for or refuse treatment with EV, including patients with uncontrolled diabetes, peripheral neuropathy grade ≥ 2 and pre-existing significant skin disorders.
This trial tested the addition of nivolumab in combination with GC and followed by nivolumab maintenance (until progression or maximum of 24 months) compared to GC alone.
Overall survival was the primary endpoint which improved to 21.4 months with avelumab compared to 14.3 months with BSC.
The response rate was improved with GC plus nivolumab (57.6% vs. 43.1%).
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