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J Clin Oncol. 2016 Sep 10;34(26):3119-25. doi: 10.1200/JCO.2016.67.9761. Epub 2016 Jun 6.

Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer.

Author information

1
Christophe Massard, Institut Gustave Roussy Cancer Centre, Villejuif, France; Michael S. Gordon, Pinnacle Oncology Hematology, Scottsdale, AZ; Sunil Sharma, Huntsman Cancer Institute, Salt Lake City, UT; Saeed Rafii, Sarah Cannon Research Institute, London, UK; Zev A. Wainberg and Alexandra Drakaki, University of California, Los Angeles; and Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA; Jason Luke and Peter H. O'Donnell, University of Chicago Comprehensive Cancer Center, Chicago, IL; Tyler J. Curiel, The University of Texas Health Science Center, San Antonio, TX; Gerardo Colon-Otero and Winston Tan, Mayo Clinic, Jacksonville, FL; Rachel E. Sanborn, Providence Cancer Center, Portland, OR; John F. Kurland, Marlon C. Rebelatto, Xiaoping Jin, John A. Blake-Haskins, and Ashok Gupta, MedImmune, Gaithersburg, MD; and Neil H. Segal, Memorial Sloan Kettering Cancer Center, New York, NY.
2
Christophe Massard, Institut Gustave Roussy Cancer Centre, Villejuif, France; Michael S. Gordon, Pinnacle Oncology Hematology, Scottsdale, AZ; Sunil Sharma, Huntsman Cancer Institute, Salt Lake City, UT; Saeed Rafii, Sarah Cannon Research Institute, London, UK; Zev A. Wainberg and Alexandra Drakaki, University of California, Los Angeles; and Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA; Jason Luke and Peter H. O'Donnell, University of Chicago Comprehensive Cancer Center, Chicago, IL; Tyler J. Curiel, The University of Texas Health Science Center, San Antonio, TX; Gerardo Colon-Otero and Winston Tan, Mayo Clinic, Jacksonville, FL; Rachel E. Sanborn, Providence Cancer Center, Portland, OR; John F. Kurland, Marlon C. Rebelatto, Xiaoping Jin, John A. Blake-Haskins, and Ashok Gupta, MedImmune, Gaithersburg, MD; and Neil H. Segal, Memorial Sloan Kettering Cancer Center, New York, NY. segaln@mskcc.org.

Abstract

PURPOSE:

To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC).

METHODS:

A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1-positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1.

RESULTS:

A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks).

CONCLUSION:

Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.

PMID:
27269937
PMCID:
PMC5569690
DOI:
10.1200/JCO.2016.67.9761
[Indexed for MEDLINE]
Free PMC Article

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