Complete Response to Pembrolizumab After Progression on Avelumab Maintenance in Metastatic Urothelial Carcinoma

Introduction: Avelumab maintenance after response to platinum chemotherapy improves outcomes in metastatic urothelial carcinoma. Progression during maintenance presents a therapeutic dilemma. Case Presentation: A 72-year-old man underwent radical cystectomy and left nephroureterectomy for high-grade urothelial carcinoma. Two and a half years later, a solitary pelvic nodal recurrence achieved complete response to gemcitabine-cisplatin, after which avelumab maintenance was started. After 16 cycles, the same node regrew, indicating progression. Pembrolizumab was initiated and induced a second complete response after four cycles. He remains recurrence-free for three years without immune-related adverse events. Conclusion: Durable remission with pembrolizumab following progression on avelumab suggests that switching from PD-L1 to PD-1 blockade can overcome resistance in selected patients; prospective studies and biomarker strategies, including PD-L2 assessment, are warranted and may guide individualized rechallenge strategies.