From the Guidelines
Yes, carboplatin and gemcitabine can be used as first-line treatment for advanced urothelial carcinoma, followed by atezolizumab as maintenance therapy, as recommended by the European Association of Urology guidelines on muscle-invasive and metastatic bladder cancer 1. This approach is particularly valuable for patients who are cisplatin-ineligible but still candidates for platinum-based chemotherapy. The typical regimen involves carboplatin (AUC 4-5) and gemcitabine (1000 mg/m²) administered on days 1 and 8 of a 21-day cycle for 4-6 cycles. For patients who achieve at least stable disease after chemotherapy, maintenance atezolizumab (1200 mg IV every 3 weeks) can then be initiated. This maintenance approach has been shown to significantly improve overall survival compared to best supportive care alone. The rationale behind this sequence is that the chemotherapy reduces tumor burden and may enhance immunogenicity, while the subsequent immunotherapy with atezolizumab helps maintain response and target residual disease by blocking PD-L1 and enhancing T-cell activity against the cancer. Some key points to consider when using this approach include:
- Patient selection: The guidelines recommend using carboplatin and gemcitabine in patients who are unfit for cisplatin but fit for carboplatin 1.
- Dosing and administration: The typical regimen involves carboplatin (AUC 4-5) and gemcitabine (1000 mg/m²) administered on days 1 and 8 of a 21-day cycle for 4-6 cycles.
- Maintenance therapy: Atezolizumab (1200 mg IV every 3 weeks) can be used as maintenance therapy in patients who achieve at least stable disease after chemotherapy.
- Monitoring and toxicity management: Patients should be monitored for immune-related adverse events during atezolizumab therapy, and treatment should continue until disease progression or unacceptable toxicity. It's worth noting that the guidelines also recommend considering the immune checkpoint inhibitors pembrolizumab and atezolizumab in cases with high PD-L1 expression for first-line treatment in patients unfit for platinum-based chemotherapy, although this is a weaker recommendation 1. Additionally, the guidelines recommend offering the immune checkpoint inhibitor pembrolizumab to patients experiencing disease progression during or after platinum-based combination chemotherapy for metastatic disease, and enfortumab vedotin as monotherapy to patients with advanced or metastatic urothelial carcinoma pretreated with platinum chemotherapy and immunotherapy 1. Overall, the use of carboplatin and gemcitabine as first-line treatment for advanced urothelial carcinoma, followed by atezolizumab as maintenance therapy, is a viable option for patients who are cisplatin-ineligible but still candidates for platinum-based chemotherapy, and should be considered in the context of the individual patient's needs and circumstances.
From the Research
Treatment Options for Advanced Urothelial Carcinoma
- Carboplatin and gemcitabine can be used as a first-line treatment for advanced urothelial carcinoma, especially in patients with impaired renal function 2, 3.
- The combination of carboplatin and gemcitabine has shown efficacy in patients with advanced urothelial carcinoma, with an overall response rate of 50% and a median survival of 13-14 months 2.
- However, the clinical outcome of carboplatin-based regimens has been reported to be unsatisfactory compared to cisplatin-based regimens 4.
Use of Atezolizumab as Maintenance Therapy
- There is no direct evidence in the provided studies on the use of atezolizumab as maintenance therapy after carboplatin and gemcitabine treatment for advanced urothelial carcinoma.
- However, atezolizumab has been approved for the treatment of advanced urothelial carcinoma, and its use as maintenance therapy may be considered based on clinical judgment and patient-specific factors.