Cabozantinib Plus Pembrolizumab Shows Promise in Treating Advanced mUC

A phase 2, single-arm trial showed that cabozantinib plus pembrolizumab exhibited a manageable toxicity profile and promising efficacy in treating patients with cisplatin-ineligible metastatic urothelial carcinoma (mUC).

The study was led by Rohit K. Jain, MD, MPH, and presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Dr. Jain and colleagues sought to determine if treatment with cabozantinib plus pembrolizumab would prove safe and efficacious for patients with treatment-naïve mUC.

The trial’s primary end point was objective response rate (ORR), with key secondary end points that included progression-free survival (PFS) and overall survival.

As a first-line treatment, the open-label, multicenter trial prescribed patients with pembrolizumab 200 mg every 3 weeks and cabozantinib 40 mg daily.

With a median follow-up period of 14.4 months (95% CI, 12.2-16.2), 35 patients evaluable for response were enrolled in the study between December 2018 and April 2023.

Researchers observed responses in 15 patients, including a complete response in 5 (14.3%) patients and an ORR of 42.8%. Ten (28.6%) patients experienced stable disease, and the disease control rate was 68.5%. The median PFS was 7.7 months (95% CI, 4.2-11.2).

Of the participating patients, 52% reported any-grade treatment-related adverse events (TRAEs) related to pembrolizumab or cabozantinib. Diarrhea, anorexia, dysgeusia, weight loss, and nausea were the most common grade 1 or 2 TRAEs. The most reported grade 3 or 4 TRAEs were hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue, with 44% of patients developing 1 of the conditions.

“This novel phase 2 trial of pembrolizumab plus cabozantinib demonstrated a manageable toxicity profile and promising efficacy as first-line therapy in mUC, including patients ineligible for cisplatin,” the researchers wrote. “Further investigation with a focus on predictive biomarkers is ongoing.”