Disitamab Vedotin in Previously Treated Patients With Advanced HER2-Positive Urothelial Carcinoma

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In a combined analysis of two Chinese phase II trials (RC48-C005 and RC48-C009) reported in the Journal of Clinical Oncology, Sheng et al found that the antibody-drug conjugate disitamab vedotin—an anti-HER2 antibody conjugated with monomethyl auristatin—produced promising results in patients with HER2-positive locally advanced or metastatic urothelial carcinoma that was refractory to standard therapies.

Study Details

In the multicenter trials, a total of 117 patients with disease progression on at least one previous line of systemic chemotherapy were enrolled between December 2017 and September 2022. Patients received disitamab vedotin at 2 mg/kg once every 2 weeks until disease progression or unacceptable toxicity. All patients had metastatic disease. The primary endpoint of the trial was objective response rate on blinded independent review committee assessment.


Confirmed objective responses were observed in 54 patients (50.5%, 95% confidence interval [CI] = 40.6%–60.3%), with complete response seen in 2 (1.9%). Consistent results were observed in subgroups including patients with liver metastasis and patients who had received previous anti–PD-1/L1 therapy. At data cutoff in May 2022, median duration of response was 7.3 months (95% CI = 5.7–10.8 months). An additional 34 patients (31.8%) had stable disease, yielding a disease control rate of 82.2%.

Median follow-up was 20.5 months. Median progression-free survival was 5.9 months (95% CI = 4.3–7.2 months), with a 12-month rate of 24.7% (95% CI = 16.5%–33.7%). Median overall survival was 14.2 months (95% CI = 9.7–18.8 months), with an 18-month rate of 42.2% (95% CI = 32.5%–51.5%).

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 64.2% of patients (grade 4 in 2.8%); most commonly, peripheral sensory neuropathy (18.7%) and neutropenia (12.1%). The most common treatment-related adverse events of any grade were peripheral sensory neuropathy (in 68.2% of patients), leukopenia (in 50.5%), increased aspartate aminotransferase (in 42.1%), and neutropenia (in 42.1%). The most common treatment-related adverse event leading to treatment discontinuation was peripheral sensory neuropathy (11.2%). No treatment-related deaths were reported.

The investigators concluded, “Disitamab vedotin demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic urothelial carcinoma who had progressed on at least one line of systemic chemotherapy.”

Aiping Zhou, MD, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Natural Science Foundation of China and by RemeGen, Ltd. For full disclosures of the study authors, visit

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