Thomas Powles, MD, PhD

In metastatic urothelial carcinoma, the bar has been set low, with a median survival of 1 year in cisplatin-eligible patients and 6 to 8 months when platinum-based therapy fails to elicit a response in patients, explained formal study discussant Thomas Powles, MD, PhD, Director, Bart’s Cancer Center, London, UK. Both atezolizumab and pembrolizumb have shown efficacy as front-line treatments of urothelial carcinoma.

“This is the first positive trial for first-line immune/chemotherapy combinations in urothelial cancer, which is an important step,” Dr. Powles said. “An overall survival advantage is needed for a widespread change in practice. This is a realistic possibility for this combination in the near future. Detail of subgroup analysis is also keenly anticipated due to the complexity of the study.”

He added, “The data from the atezolizumab monotherapy arm are exciting and strengthen the case for atezolizumab in patients with high expression of PD-L1 (programmed cell death ligand 1). Only 24% of patients with metastatic urothelial cancer have high PD-L1 expression, and we need proper patient selection. This drug is well tolerated, with a grade 3 to 5 adverse event rate of 16% compared with 82% for the combination arm.”

Dr. Powles emphasized that the PD-L1 biomarker “did not work for the combination or in the second-line setting with concurrent chemotherapy.” ■

DISCLOSURE: Dr. Powles reported financial relationships with AstraZeneca, Roche, Exelixis, Bristol-Myers Squibb, Novartis, Pfizer, Merck Sharp & Dohme, and Ipsen.