Real‐world effectiveness and safety of RC48‐ADC alone or in combination with PD‐1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study

Abstract Introduction Previous RC48 (Disitamab Vedotin) studies established that the safety and efficacy of RC48‐antibody–drug conjugate (ADC), either alone or combined with toripalimab, for metastatic urothelial carcinoma (mUC) patients exhibiting human epidermal growth factor receptor 2 (HER2)‐positive or even HER2‐negative status after standard chemotherapy failure. Methods With locally advanced or metastatic urothelial carcinoma (la/mUC), patients who received RC48‐ADC monotherapy or a combination with programmed cell death protein 1 (PD‐1) inhibitors between August 2021 and October 2022 were enrolled in this retrospective observational study to evaluate the real‐world antitumor effectiveness and safety. Results Among the 38 enrolled patients (29 males; median age 67.5 years [38–93]), 8 received RC48‐ADC monotherapy, while 30 received combination therapy. Initially, 63.2% (24/38) of the patients had received ≥1 line of prior treatment, and 63.2% (24/38) had visceral metastasis. UC of the bladder represented the majority type in 68.4% (26/38) of cases. By the data cutoff in March 2023, the overall objective response rate (ORR) was 63.2% (95% CI, 47.1%–79.2%), with a disease control rate (DCR) of 89.5% (95% CI, 79.3%–99.7%). Median follow‐up time was 10.6 months. The median progression‐free survival (PFS) was 8.2 months (95% CI, 5.9–10.5), with a 6‐month PFS rate of 63.2% and a 12‐month PFS rate of 34.1%. Median overall survival (OS) was not reached, with a 12‐month OS rate of 76.7%. The median duration of response was 7.3 months (95% CI, 4.6–10.0) among 24 patients evaluated as partial response (PR). The most common treatment‐related adverse events (TRAEs) included anemia (71.1%), anorexia (57.9%), asthenia (52.6%), hypoesthesia (52.6%), bone marrow suppression (47.4%), alopecia (47.4%), nausea (44.7%), proteinuria (36.8%), vomiting (34.2%), and hypoalbuminemia (31.6%). No patient experienced TRAEs of Grade ≥3. One patient had an immune‐related adverse event (irAE) of rash related to toripalimab. Conclusions Both as monotherapy and in combination with PD‐1 inhibitors, RC48‐ADC exhibits promising effectiveness and manageable safety profile for mUC patients in real‐world settings.