Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.

Purpose
We assessed the safety and antitumor activity of avelumab, a fully human anti–programmed deathlig and 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma.

Methods
In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2weeks. The primary objectiveswere safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST]
version 1.1), progression-free survival, overall survival (OS), and PD-L1–associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on $ 5% of tumor cells.

Results
Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1–positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%).

Conclusion
Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

Read an Expert Commentary by Bishoy Faltas on this Abstract 

J Clin Oncol 35:2117-2124. © 2017 by American Society of Clinical Oncology.

Andrea B. Apolo, Jeffrey R. Infante, Ani Balmanoukian, Manish R. Patel, Ding Wang, Karen Kelly, Anthony E. Mega, Carolyn D. Britten, Alain Ravaud, Alain C. Mita, Howard Safran, Thomas E. Stinchcombe, Marko Srdanov, Arnold B. Gelb, Michael Schlichting, Kevin Chin, and James L. Gulley
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