What is the next step in treatment for a patient with advanced urothelial carcinoma who has had a partial response to six cycles of gemcitabine (Gemzar) and cisplatin (Platinol) chemotherapy?

Maintenance Avelumab is the Recommended Next Step After Partial Response to Gemcitabine and Cisplatin in Advanced Urothelial Carcinoma

For a patient with advanced urothelial carcinoma who has had a partial response to six cycles of gemcitabine and cisplatin chemotherapy, maintenance avelumab should be initiated within 10 weeks of chemotherapy completion.

Rationale for Maintenance Therapy

• Maintenance avelumab is the standard of care for patients who achieve stable disease or better (complete or partial response) after 4-6 cycles of platinum-based chemotherapy 1, 2
• Avelumab maintenance therapy significantly prolongs overall survival compared to best supportive care alone (median OS 21.4 months vs. 14.3 months; HR 0.69,95% CI 0.56-0.86) 2
• The JAVELIN Bladder 100 trial demonstrated an increase in median overall survival from 14 months to 21 months with avelumab maintenance 1, 2
• Treatment should be initiated within 10 weeks of completing first-line platinum-based chemotherapy 1

Implementation Guidelines

• Avelumab maintenance should be continued until disease progression 1
• The benefit of avelumab maintenance is seen regardless of PD-L1 status, though the benefit is more pronounced in PD-L1-positive tumors 2
• Median progression-free survival with avelumab maintenance is 3.7 months vs 2.0 months with best supportive care alone 2

Alternative Options (Not Recommended as First Choice)

• Continuation maintenance with gemcitabine alone is mentioned in some guidelines but has less robust evidence compared to avelumab maintenance 1
• Close observation without therapy is not recommended as it has been shown to be inferior to maintenance avelumab in terms of overall survival 2

Special Considerations

• If disease progression occurs on avelumab maintenance, subsequent treatment options include:
  • Enfortumab vedotin (especially if not previously used) 1, 3
  • Erdafitinib for patients with FGFR2/3 genetic alterations 3
  • Single-agent chemotherapy (docetaxel, paclitaxel, or vinflunine) 1

Common Pitfalls to Avoid

• Delaying initiation of maintenance therapy beyond 10 weeks after chemotherapy completion may reduce efficacy 1
• Discontinuing maintenance therapy prematurely (before progression) is not recommended as the survival benefit is dependent on continued treatment 1
• Failing to monitor for immune-related adverse events, which can occur with avelumab therapy 2

Monitoring During Maintenance Therapy

• Regular assessment for treatment-related adverse events, particularly immune-mediated reactions 2
• Scheduled imaging studies to evaluate for disease progression 1
• The incidence of adverse events grade 3 or higher with avelumab maintenance is 47.4% compared to 25.2% with best supportive care alone 2

By implementing maintenance avelumab after a partial response to gemcitabine and cisplatin, you can significantly improve overall survival outcomes in patients with advanced urothelial carcinoma.