Posted: Friday, September 30, 2022
According to research presented in the Journal of Clinical Oncology, a combination treatment of soluble EphB4-human serum albumin (EphB4-HSA) and pembrolizumab may be an efficacious treatment option for some patients with metastatic urothelial carcinoma. This treatment pair resulted in improvements in survival and clinical outcomes and was associated with acceptable toxicity. In addition, a phase II study of the combination in this patient population is under way, and it includes a front-line cohort and an EphrinB2-positive biomarker-selected previously treated cohort (ClinicalTrials.gov identifier NCT04486781).
“Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy,” noted Sarmad Sadeghi, MD, PhD, of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and colleagues. “Immune checkpoint [PD-1/PD-L1] antibodies have low response rates, and thus there exists a major unmet need.”
The phase II study included 70 patients with metastatic urothelial carcinoma who experienced disease recurrence or progression after undergoing platinum-based chemotherapy. At a median follow-up of 22.9 months, the median overall survival and progression-free survival were 14.6 months and 4.1 months, respectively. The objective response rate was 37% (n = 26). Among the 46 patients (66%) who tested positive for EphrinB2 expression, median overall survival was 21.5 months, and median progression-free survival was 5.7 months. In this patient subgroup, the overall response rate was 52%, with 11 patients (24%) achieving a complete response. At follow-ups of 6, 12, and 24 months, a respective 88%, 74%, and 69% of patients maintained their responses.
Overall toxicity was determined to be acceptable. Hypertension was the most frequent adverse event attributed to the investigative therapy. According to the study authors, this toxicity was managed by initiating or modifying the antihypertensive regimen.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.