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JAMA Oncol. 2017 Sep 14;3(9):e172411. doi: 10.1001/jamaoncol.2017.2411. Epub 2017 Sep 14.

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

Author information

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

Abstract

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.

PMID:
28817753
PMCID:
PMC5824288
DOI:
10.1001/jamaoncol.2017.2411
[Indexed for MEDLINE]
Free PMC Article

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