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Original Investigation
September 14, 2017

Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study

Author Affiliations
  • 1Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, England
  • 2Department of Medicine, University of Chicago Comprehensive Cancer Center, Chicago, Illinois
  • 3Department of Cancer Medicine, Institut Gustave Roussy Cancer Centre, Villejuif, France
  • 4Drug Development Unit, Sarah Cannon Research Institute, University College London Cancer Centre, London, England
  • 5Division of Genitourinary Medical Oncology, University of California, San Francisco Medical Center
  • 6School of Medicine, Case Western Reserve University Seidman Cancer Center, Cleveland, Ohio
  • 7Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
  • 8Department of Medicine, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
  • 9Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  • 10Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas
  • 11Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, Florida
  • 12Division of Medical Oncology, Stanford University, Stanford, California
  • 13Department of Medicine, Augusta University, Augusta, Georgia
  • 14Immuno-Oncology Clinical Development, MedImmune, Gaithersburg, Maryland
  • 15Immuno-Oncology Clinical Development, AstraZeneca, Gaithersburg, Maryland
  • 16Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
JAMA Oncol. 2017;3(9):e172411. doi:10.1001/jamaoncol.2017.2411
Key Points

Question  Does durvalumab provide clinical benefit to patients with locally advanced or metastatic urothelial carcinoma (UC)?

Findings  In a phase 1/2 open-label study of 191 patients with locally advanced/metastatic UC, confirmed objective response rate with durvalumab, 10 mg/kg every 2 weeks, was 17.8%, including 7 complete responses, and median progression-free survival and overall survival were 1.5 and 18.2 months, respectively. Grade 3/4 treatment-related and immune-mediated adverse events occurred in 13 patients (6.8%) and 4 patients (2.1%), respectively.

Meaning  Durvalumab shows favorable efficacy and an excellent safety profile in patients with locally advanced/metastatic UC.


Importance  The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval.

Objective  To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC.

Design, Setting, and Participants  This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein.

Intervention  Patients were administered durvalumab intravenous infusion, 10 mg/kg every 2 weeks, for up to 12 months or until progression, starting another anticancer therapy, or unacceptable toxic effects.

Main Outcomes and Measures  Primary end points were safety and confirmed objective response rate (ORR) per blinded independent central review (Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1).

Results  A total of 191 patients with UC had received treatment. As of October 24, 2016 (90-day update), the median follow-up was 5.78 months (range, 0.4-25.9 months). The median age of patients was 67.0 years and most were male (136 [71.2%]) and white (123 [71.1%]). All patients had stage 4 disease, and 190 (99.5%) had prior anticancer therapy (182 [95.3%] postplatinum). The ORR was 17.8% (34 of 191; 95% CI, 12.7%-24.0%), including 7 complete responses. Responses were early (median time to response, 1.41 months), durable (median duration of response not reached), and observed regardless of programmed cell death ligand-1 (PD-L1) expression (ORR, 27.6% [n = 27; 95% CI, 19.0%-37.5%] and 5.1% [n = 4; 95% CI, 1.4%-12.5%] in patients with high and low or negative expression of PD-L1, respectively). Median progression-free survival and overall survival were 1.5 months (95% CI, 1.4-1.9 months) and 18.2 months (95% CI, 8.1 months to not estimable), respectively; the 1-year overall survival rate was 55% (95% CI, 44%-65%), as estimated by Kaplan-Meier method. Grade 3/4 treatment-related adverse events (AEs) occurred in 13 patients (6.8%); grade 3/4 immune-mediated AEs occurred in 4 patients (2.1%); and treatment-related AEs led to discontinuation of 3 patients (1.6%), 2 of whom had immune-mediated AEs that led to death (autoimmune hepatitis and pneumonitis).

Conclusions and Relevance  Durvalumab, 10 mg/kg every 2 weeks, demonstrates favorable clinical activity and an encouraging and manageable safety profile in patients with locally advanced/metastatic UC.

Trial Registration  clinicaltrials.gov Identifier: NCT01693562