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J Clin Oncol. 2017 Jul 1;35(19):2117-2124. doi: 10.1200/JCO.2016.71.6795. Epub 2017 Apr 4.

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

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Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.


Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 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 2 weeks. The primary objectives were 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.

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