Case Study: HER2-Targeting Drug Plus Pembrolizumab for Third-Line Metastatic UC

By Zachary Bessette - December 12, 2022

A newly published case report may signify a promising novel antitumor strategy in locally advanced or metastatic urothelial carcinoma (UC).

While systemic chemotherapy has been traditionally considered the standard of care for locally advanced or metastatic UC, novel immune checkpoint inhibitors and antibody-drug conjugates have demonstrated efficacy in this setting in recent years.

Researchers from the Department of Abdominal Oncology in the West China Hospital at Sichuan University reported on a systemic therapy approach for a male aged 68 years with human epidermal growth factor receptor 2 (HER2)-positive, programmed death-ligand 1 (PD-L1)-negative metastatic UC. The patient had renal insufficiency, numerous metastases, and had not responded to first-line platinum-based chemotherapy or second-line treatment with pembrolizumab plus trastuzumab.

As a third-line treatment approach, the patient received RC48—a HER2-targeting antibody-drug conjugate—combined with pembrolizumab. A rapid partial response was observed in the initial evaluation.

In subsequent positron emission tomography/computed tomography imaging, a complete response was found and progression-free survival of greater than 12 months was noted.

Additionally, researchers reported no grade 3 or 4 treatment-related adverse events or aggravations of renal insufficiency during the third-line therapy.

“Although our report was only a case, it showed a significant difference in the efficacy of anti-HER2 drugs for UC,” study authors concluded, adding that RC48 combined with immunotherapy is worth further exploration in the fist-line setting for patients with locally advanced or metastatic UC.