RC48-ADC monotherapy or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma with HER2 low and null expression: a multicenter, real-world, retrospective study

Abstract

BACKGROUND: Approximately half of urothelial carcinoma (UC) patients exhibit low or null HER2 expression. Limited data are available on the efficacy of anti-HER2 RC48-ADC (Disitamab Vedotin) in HER2 low and null advanced UC. METHODS: Patients with locally advanced or metastatic UC (la/mUC) with HER2 low (IHC 1+) and null (IHC 0) expression who received RC48-ADC monotherapy or in combination with programmed cell death protein 1 (PD-1) inhibitors were enrolled in this multi-center, retrospective study. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: A total of 27 patients were included, with a median age of 64 years, and 17 (63%) were male. Seven (26.0%) patients received RC48-ADC alone, and 20 (74.1%) received RC48-ADC combined with a PD-1 inhibitor. Eight (30.8%) patients achieved partial response (PR), and twelve (46.2%) exhibited stable disease (SD). The ORR was 30.8%, and DCR was 76.9%. The median PFS and OS were 7.4 months and 13.8 months, one-year PFS and OS rates were 29.1% and 57.2%, respectively. Both RC48 monotherapy and combination were well-tolerated. Grade 3 AEs occurred in 4 (14.8%) patients received combination treatment, including 2 cases of anemia, 1 case of increased serum creatinine, and 1 case of autoimmune encephalitis. No grade 3 or higher AEs were observed in RC48-ADC monotherapy. CONCLUSION: RC48-ADC demonstrated favorable efficacy and manageable safety in la/mUC patients with HER2 low and null expression in real-world settings. Prospective studies with large sample size are warranted to validate this finding.

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