Disitamab vedotin alone or in combination with immune checkpoint inhibitors in bladder-sparing treatment of muscle-invasive bladder cancer: a real-world study

Abstract

Purpose

To evaluate the efficacy and safety of a novel humanized anti-HER2 antibody, RC48-ADC (Disitamab vedotin, DV), the combination of RC48-ADC with PD-1 inhibitors was used to treat muscle-invasive bladder cancer (MIBC). This combination therapy has potential applications in both bladder preservation and neoadjuvant therapy for MIBC.

Methods

Patients with MIBC underwent transurethral resection of bladder tumors followed by RC48-ADC alone or in combination with PD-1 inhibitors. Radiological and endoscopic evaluations were conducted three months later. The primary endpoint was objective response rate (ORR), with secondary endpoints including complete response rate (CR), partial response rate (PR), and bladder preservation rate. Treatment safety was assessed according to RECIST v1.1 criteria.

Results

Eleven patients were enrolled, with a median follow-up of 19.0 months. Nine patients achieved objective response, including six CR and three PR cases. The pathological ORR was 81.8%. Eight patients continued combined treatment after three months, maintaining a 72.7% bladder preservation rate at sixteen months. One elderly patient progressed from ypT2N0M0 to ypT3N0M0 and underwent radical cystectomy but had no recurrence or metastasis twelve months post-operation. All patients reported varying degrees of treatment-related adverse reactions, which were largely manageable.

Conclusion

The combination of RC48-ADC and PD-1 inhibitors proves to be a viable and safe option for bladder-sparing therapy, particularly for T2-stage MIBC patients who are ineligible for surgery and chemotherapy. This approach offers a promising new direction for bladder preservation or neoadjuvant therapy in MIBC patients.

Micro-Abstract

The measures of bladder protection in muscle-invasive bladder cancer (MIBC) need to be improved. RC48-ADC is a new type of monoclonal antibody against HER2, which shows significant effect in advanced urothelial cancer, but is rarely used in non-metastatic MIBC. We tried to combine RC48-ADC with PD-1 inhibitors for bladder preservation or neoadjuvant therapy for MIBC. The bladder retention rate of MIBC treated with RC48-ADC combined with PD-1 inhibitors could still reach 72.7% after 16 months. Other patients can be treated with radical cystectomy, which does not affect the prognosis. RC48-ADC combined with PD-1 inhibitors can be used as bladder-preserving therapy or neoadjuvant therapy for MIBC.