Divergent Responses to Enfortumab Vedotin and Pembrolizumab in Concurrent Urothelial and Renal Cell Carcinoma: Case Report and Literature Review.

Abstract

Introduction: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of metastatic urothelial carcinoma (UC) and renal cell carcinoma (RCC). However, these cancers may exhibit divergent responses to the same immunotherapy.

Case presentation: Here, we report a case of a patient with concurrent stage 4 UC and resected stage III clear cell RCC (ccRCC) who experienced complete remission of UC following treatment with enfortumab vedotin (EV) and pembrolizumab but developed hyperprogression of metastatic RCC. The decision was made to discontinue ICIs and initiate a combination therapy of lenvatinib (VEGF receptor inhibitor) and everolimus (mTOR inhibitor). The patient exhibited a complete radiographic response to this combination therapy, with no significant side effects, and has remained well 18 months after the onset of hyperprogression in ccRCC.

Conclusion: We highlight the role of distinct immune microenvironments in mediating differential responses to immunotherapy, in patients with coexisting UC and ccRCC. We underscore the importance of personalized treatment strategies in patients with dual malignancies, particularly when divergent responses to immunotherapy are observed, offering durable responses while avoiding the risks associated with continued immune checkpoint inhibition.