TY - JOUR
T1 - Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer
AU - Massard, Christophe
AU - Gordon, Michael S.
AU - Sharma, Sunil
AU - Rafii, Saeed
AU - Wainberg, Zev A.
AU - Luke, Jason
AU - Curiel, Tyler J.
AU - Colon-Otero, Gerardo
AU - Hamid, Omid
AU - Sanborn, Rachel E.
AU - O'Donnell, Peter H.
AU - Drakaki, Alexandra
AU - Tan, Winston
AU - Kurland, John F.
AU - Rebelatto, Marlon C.
AU - Jin, Xiaoping
AU - Blake-Haskins, John A.
AU - Gupta, Ashok
AU - Segal, Neil H.
N1 - Funding Information:
Supported by MedImmune. Genentech (Inst), GlaxoSmithKline (Inst), Abbvie (Inst), Merck Serono (Inst), MedImmune (Inst), Incyte (Inst), OncoMed Pharmaceuticals (Inst), Pfizer (Inst), Array BioPharma (Inst), Amgen (Inst), Eli Lilly (Inst), Lilly/ImClone (Inst), Millennium Pharmaceuticals (Inst), Gilead Sciences (Inst), Sirtex Medical (Inst), Calithera Biosciences (Inst) Novartis (Inst), Spectrum Pharmaceuticals (Inst), GlaxoSmithKline (Inst), Merrimack Pharmaceuticals (Inst), Millennium Pharmaceuticals (Inst), Amgen (Inst), Labceutics (Inst), Mirati Therapeutics (Inst), MedImmune (Inst), Johnson and Johnson (Inst), Gilead Sciences (Inst), Plexxikon (Inst), Celgene (Inst), Sanofi (Inst), Merck (Inst), Onyx Pharmaceuticals (Inst), Bayer AG (Inst), Blueprint Medicines (Inst), XuanZhu Pharma (Inst), Incyte (Inst), LSK BioPharma (Inst) Novartis (Inst), Plexxikon (Inst), Pfizer (Inst), BioMarin (Inst), Merck (Inst) Novartis, EMD Serono, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Boston Biomedical, MedImmune, Incyte, Celldex, Genentech Novartis (Inst) Bristol-Myers Squibb (Inst), MedImmune (Inst), Merck Boehringer Ingelheim (Inst) Novartis MedImmune, Bristol-Myers Squibb, Pfizer, Genentech, Merck We thank all the patients and investigators who participated in the trial. We also thank Colleen Maher (Memorial Sloan Kettering Cancer Center, New York, NY) for her contributions to enrollment and study management. Thea Goberville, PhD, provided writing and editorial support.
Publisher Copyright:
© 2016 by American Society of Clinical Oncology.
PY - 2016/9/10
Y1 - 2016/9/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2016.67.9761
DO - 10.1200/JCO.2016.67.9761
M3 - Article
C2 - 27269937
AN - SCOPUS:84989918072
VL - 34
SP - 3119
EP - 3125
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 26
ER -