Trastuzumab Biosimilar Plus Paclitaxel Shows Promise for Patients With HER2-Positive Recurrent or Metastatic Urothelial Carcinoma

According to an open-label, single-arm phase 2 study, the trastuzumab biosimilar, trastuzumab-pkrb, plus paclitaxel showed promising efficacy and manageable toxicity among patients with HER2-positive recurrent or metastatic urothelial carcinoma.

This phase 2 study enrolled 27 patients with HER2-positive recurrent or metastatic urothelial carcinoma. All patients had previously been treated with gemcitabine plus cisplatin or carboplatin, and 74% had previously been treated with immune checkpoint inhibitors. All patients received an initial dose of 8 mg/kg of the trastuzumab biosimilar on day 1, followed by 6 mg/kg on day 1 every 3 weeks, plus 175 mg/m² paclitaxel on day 1 every 3 weeks. After 6 cycles, patients received monotherapy with the trastuzumab biosimilar until disease progression, unacceptable tolerability, or up to 2 years. The primary end point was overall response rate (ORR), with secondary end points including overall survival, progression-free survival, and safety.

With a median follow-up duration of 10.5 months, 26 of the 27 enrolled patients were evaluable for treatment response. The ORR was 48.1%, with 1 patient achieving a complete response and 12 achieving a partial response. With an additional 10 patients with stable disease, and 3 with progressive disease, the disease control rate was 85.1%. The median duration of response was 6.9 months. The progression-free survival was 8.4 months, and the overall survival was 13.5 months.

All 27 patients that received at least 1 cycle of the study treatment were included in the safety assessment. The most common treatment-related adverse event of any grade was peripheral neuropathy, in 88.9% of patients. The most common grade ≥3 treatment related adverse event was neutropenia (25.9%). There was 1 death, due to sepsis. Of all patients, 3.7% discontinued permanently, and 25.9% experienced a dose interruption.

Study authors concluded, “we found that trastuzumab-pkrb plus paclitaxel has promising efficacy…in patients with HER2 overexpressing [urothelial carcinoma] who failed platinum-based chemotherapy. Toxicities were manageable and generally well-tolerated, as reported for breast cancer.”

Source:

Kim M, Lee JL, Shin SJ, et al. Phase II study of a trastuzumab biosimilar in combination with paclitaxel for HER2-positive recurrent or metastatic urothelial carcinoma: KCSG GU18-18. ESMO Open. Published online June 17, 2023. doi:10.01016/j.esmoop.2023.101588