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Thomas Flaig, MD


Sequential HER2-Targeted Antibody-Drug Conjugate in Resistant Metastatic Bladder Cancer: Case Study

By: Joshua Swore, PhD
Posted: Monday, April 3, 2023

HER2-targeting antibody-drug conjugates may prove to be effective in the treatment of patients with HER2-amplified metastatic bladder cancer, according to a case study presented in JCO Precision Oncology. “Platinum-based chemotherapy remains the gold standard for metastatic bladder cancer treatment. In the past decade, immune checkpoint inhibitors and targeted therapies have been added to the therapeutic arsenal of metastatic bladder cancer,” said Denis L. Jardim, MD, PhD, of Hospital Sírio-Libanês, São Paulo, and colleagues. “Among these new therapeutic modalities, targeting HER2 alterations has gained prominence and emerged as a potential strategy.”

The case study featured an 84-year-old, nonsmoking, male patient with intermittent macroscopic hematuria. Resection of a bladder tumor yielded a diagnosis of muscle-invasive urothelial cancer. Based on the patient’s profile, the providers opted for concurrent chemoradiotherapy plus image-guided radiation therapy and weekly cisplatin. At 6 months after platinum therapy, the patient presented with metastatic recurrence in retroperitoneal and pelvic lymph nodes, along with bone lesions. Next-generation sequencing revealed a tumor burden of 13 mutations per megabase and notable HER2 amplification. The providers confirmed HER2 amplification using immunohistochemistry.

Following platinum therapy, the team provided the patient with nivolumab every 2 weeks. However, the patient continued to experience disease progression and was admitted to the hospital because of deterioration. In response, the providers treated the patient with ado-trastuzumab emtansine (T-DM1) once every 3 weeks, with significant clinical improvement that allowed hospital discharge, but new mediastinal nodules were reported. Following a brief pause in treatment, the patient received fam-trastuzumab deruxtecan-nxki (T-DXd). This treatment demonstrated a partial response in bone lesions and no evidence of active metabolic lesions. Furthermore, the authors reported no treatment-related adverse events, and the patient was continuing to receive therapy 2.5 years after the initial diagnosis.

Disclosure: For full disclosures of the study authors, visit

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