膀胱癌在所有癌症中約占了3%，當中有將近九成為泌尿上皮癌，過去傳統治療以鉑金類藥物的化學療法為主，對於治療失敗或復發轉移的病人，則改以紫杉醇類、pemetrexed 及vinflunine 等作為二線治療，然而，無論是腫瘤反應率或中位數存活期，皆未看到顯著效益。隨著臨床試驗結果陸續發表，免疫檢查點抑制劑 (immune checkpoint inhibitors, ICIs) 被證實可改善泌尿上皮癌的預後。根據IMvigor130及KEYNOTE-130，未接受治療的轉移性泌尿上癌病人，無論是單獨給予atezolizumab 或pembrolizumab治療，還是併用傳統化學療法，可明顯改善無惡化存活期，然而，整體存活期 (overall survival, OS) 皆無顯著差異。根據IMvigor211 及KEYNOTE-045，接受傳統化學療法失敗的轉移性泌尿上皮癌 (metastatic urothelial carcinoma, mUC) 病人，atezolizumab 無論是無惡化存活期，還是OS，皆無明顯改善，但是pembrolizumab 顯著改善OS。此外，根據CheckMate 032 試驗結果發現，一線治療失敗的mUC 病人，nivolumab 無論是客觀反應率，還是無惡化存活期，皆有不錯的效果出現，其中又以合併療法最為顯著。儘管研究結果有所差異，但是對於不適合接受傳統化學療法或無法耐受副作用的病人，抑或是已接受化學療法，還是持續惡化或復發者，仍可提供另一治療選擇。Avelumab 作為泌尿上皮癌病人一線治療後的維持治療，無論是無惡化存活期，還是OS，皆有顯著效果。本文綜參目前ICIs 用於泌尿上皮癌治療之相關臨床研究，提供臨床用藥參考。

 

Bladder cancer accounts for approximately 3% of all new cancer diagnoses, of which almost 90% are urothelial carcinoma (UC). Platinum-based chemotherapy (PBC) has long been used as the standard first-line treatment for metastatic UC (mUC). For patients who are not eligible for first-line chemotherapy, taxanes, pemetrexed, and vinflunine are given as second-line therapies. However, second-line therapy did not significantly improve the objective response rate (ORR) or the overall survival (OS) of patients. According to the results of recent clinical trials IMvigor130 and KEYNOTE-130, single treatment with atezolizumab or pembrolizumab, or combination therapy with chemo therapy, progression-free survival (PFS) and OS have been improved in untreated mUC patients. The results of these trials also showed that for patients had failed in chemo therapy, atezolizumab did not improve neither PFS nor OS. But for pemprolizumab, OS had shown to be improved significantly. Moreover, in CheckMate 032 trial, nivolumab provides a positive effect in mUC patients who had failed in first-line chemotherapy. Nivolumab can improve both ORR and PFS, and combination therapy works more effectively. Despite conflicting study results, these immunotherapies provide another treatment option for patients who are not eligible for chemotherapy. Avelumab, a maintenance therapy after first-line treatment for patients with UC, can improve PFS and OS. This article summarizes the findings of the current clinical research on ICIs for the treatment of UC and provides a reference for clinical practice.

 

 

Submitted for publication: 2022.11.23; Accepted for publication: 2023.5.31