First-Line Treatment of Advanced Renal Pelvis Cancer in Cisplatin-Eligible Patients with Adequate Renal Function (eGFR >50 ml/min) Ineligible for Enfortumab Vedotin plus Pembrolizumab
Clinical Scenario
This protocol addresses patients with upper urinary tract urothelial carcinoma (UTUC) — including renal pelvis cancer — presenting with advanced or metastatic disease who are not eligible for enfortumab vedotin plus pembrolizumab as first-line therapy.
Cisplatin suitability in this setting requires confirmation of all of the following criteria:
- ECOG PS 0–1
- eGFR >50 ml/min
- Audiometric hearing loss <grade 2
- Peripheral neuropathy <grade 2
- NYHA cardiac class <III
Role of Renal Function
Adequate renal function — eGFR >50 ml/min — is a prerequisite for cisplatin eligibility and directly determines which first-line regimen is appropriate in this setting.
Patients who meet this threshold, along with the other eligibility criteria above, are candidates for a cisplatin-based first-line approach. Those who fall below this threshold are managed differently and are not addressed by this protocol.
Treatment Approach (Partial Overview)
First-line treatment for eligible patients involves cisplatin-based combination chemotherapy. Certain regimen options include an immune checkpoint inhibitor added to the chemotherapy backbone. For patients who do not experience disease progression on first-line platinum-based chemotherapy, a maintenance immunotherapy strategy may be considered. The complete regimen options, selection criteria, and sequencing are detailed in the structured protocol.
References
DOI: 10.1016/j.eururo.2025.02.023
- First-line treatment for platinum-eligible patients unsuitable/ineligible for EV + P.
- Offer cisplatin-based chemotherapy with gemcitabine/cisplatin or HD-MVAC to cisplatin-eligible patients.
- Offer cisplatin-based chemotherapy with gemcitabine-cisplatin + nivolumab to cisplatin-eligible patients.
- A phase 3 RCT in advanced/metastatic UC has now revealed an overall benefit from addition of nivolumab to chemotherapy (gemcitabine-cisplatin), with improvements in median OS (21.7 vs 18.9 mo; HR 0.78) and median PFS (7.9 vs 7.6 mo; HR 0.72).
- Offer maintenance avelumab to patients who did not have disease progression after 4–6 cycles of platinum-based combination chemotherapy.
- Avelumab maintenance therapy after 4–6 cycles of gemcitabine plus cisplatin or carboplatin (started within 10 wk of completion of first-line PBC) significantly prolonged OS in comparison to best supportive care alone for patients with advanced or metastatic UC who did not experience disease progression during, or responded to, first-line chemotherapy.
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