目标：我们的研究旨在评估Disitamab Vedotin (DV，RC48-ADC)的疗效和安全性，这是一种采用可降解的肽链连接物将创新的人源化抗HER2抗体与破坏微管的抗有丝分裂药物monomethyl auristatin E (MMAE)结合的治疗方法。该治疗方法结合了免疫检查点抑制剂，作为对局部和局部晚期膀胱尿路上皮癌患者的保膀治疗方法的一部分。 患者和方法：我们进行了一项两个中心的实际研究，涉及局部晚期泌尿上皮癌（UC）患者。患者根据HER2表达情况（IHC 3+/2+/1+）或HER2表达缺乏（IHC 0）进行分类。主要终点是客观缓解率（ORR），由调查者根据RECIST V1.1标准评估。次要终点包括病理完全缓解率（pCR），病理部分缓解率（pPR）和病理稳定病（pSD），以及无复发存活期（RFS），病理分期降级率和治疗的安全性状况。 结果：在这项研究中，共纳入了9名患者，随访时间的中位数为12.0个月。整体确认的ORR为88.9％，5名患者达到完全缓解（CR），3名患者达到部分缓解（PR）。放射学完全缓解（rCR）与病理完全缓解（pCR）完全一致。放射学无进展生存期（rPFS）的中位数为12.0个月（范围从8.0到17.0个月）。1名患者确诊为疾病进展（PD），接受了根治性膀胱切除术。病理分期从T2N0M0进展到T3aN2M0，随后进行了加临床化疗，采用gemcitabine-cisplatin（GC）组合放疗。在9个月的随访中，未观察到复发或转移。这些患者的并发症率和程度可控，没有4级和5级不良事件的证据。 结论：DV与PD-1的联合在具有HER2 IHC 0/1+/2+/3+肌层侵袭性膀胱癌（MIBC）的患者中显示出显著的客观缓解率（ORR），同时也具有迄今报道的最长中位放射学无进展生存期（rPFS）。在治疗持续时间延长的情况下，DV加PD-1的安全性状况也得到了确认。版权所有©2023 Wei, Zhang, Yu, Hong, Lin, Li and Chen.

Objective: Our study aims to assess the effectiveness and safety profile of Disitamab Vedotin (DV, RC48-ADC), an innovative humanized anti-HER2 antibody conjugated with tubulin-disrupting antimitotic drug monomethyl auristatin E (MMAE) via a cleavable peptide linker. This treatment combined immune checkpoint inhibitors as part of the bladder sparing approach for selected patients suffering from locally and locally advanced bladder urothelial carcinoma. Patients and methods: We conducted a two-center, real-world study involving locally advanced urothelial carcinoma (UC) patients. Patients were classified based on HER2 expression (IHC 3+/2+/1+) or lack of HER2 expression (IHC 0). The primary endpoint was the objective response rate (ORR), assessed by the investigator following the criteria of RECIST V1.1. Secondary endpoints encompassed the pathological complete response rate (pCR), pathological partial response rate (pPR), and pathological stable disease (pSD), along with recurrence-free survival (RFS), the pathological downstaging rate, and the safety profile of the treatment. Results: In this study, nine patients were enrolled, with a median follow-up duration of 12.0 months. The overall confirmed ORR was 88.9%, Five patients achieved a complete response (CR), and three patients achieved a partial response (PR). The radiological complete response (rCR) aligned perfectly with pCR. The median radiological progression-free survival (rPFS) spanned 12.0 months (range from 8.0 to 17.0 months). One patient diagnosed with disease progression (PD) underwent a radical cystectomy. The pathological stage evolved from T2N0M0 to T3aN2M0, followed by adjuvant chemotherapy with a gemcitabine-cisplatin (GC) combination radiotherapy. At the 9-month follow-up, neither recurrence nor metastasis was observed. The rate and intensity of complications were manageable among these patients, with no evidence of grade 4 and 5 adverse events. Conclusion: The combination of DV and PD-1 demonstrated considerable activity in the objective response rate (ORR) in patients with HER2 IHC 0/1+/2+/3+ muscle-invasive bladder cancer (MIBC), along with the longest reported median radiological progression-free survival (rPFS) to date. With an extended duration of treatment, the safety profile of DV plus PD-1 was also confirmed to be manageable.Copyright © 2023 Wei, Zhang, Yu, Hong, Lin, Li and Chen.