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

Publication ,  Journal Article
Powles, T; O'Donnell, PH; Massard, C; Arkenau, H-T; Friedlander, TW; Hoimes, CJ; Lee, JL; Ong, M; Sridhar, SS; Vogelzang, NJ; Fishman, MN ...
Published in: JAMA Oncol
September 14, 2017

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.

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Published In

JAMA Oncol

DOI

EISSN

2374-2445

Publication Date

September 14, 2017

Volume

3

Issue

9

Start / End Page

e172411

Location

United States

Related Subject Headings

  • Survival Rate
  • Retreatment
  • Response Evaluation Criteria in Solid Tumors
  • Neoplasm Staging
  • Middle Aged
  • Male
  • Liver Neoplasms
  • Humans
  • Follow-Up Studies
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Powles, T., O’Donnell, P. H., Massard, C., Arkenau, H.-T., Friedlander, T. W., Hoimes, C. J., … Hahn, N. M. (2017). Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol, 3(9), e172411. https://doi.org/10.1001/jamaoncol.2017.2411
Powles, Thomas, Peter H. O’Donnell, Christophe Massard, Hendrik-Tobias Arkenau, Terence W. Friedlander, Christopher J. Hoimes, Jae Lyun Lee, et al. “Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study.JAMA Oncol 3, no. 9 (September 14, 2017): e172411. https://doi.org/10.1001/jamaoncol.2017.2411.
Powles T, O’Donnell PH, Massard C, Arkenau H-T, Friedlander TW, Hoimes CJ, et al. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411.
Powles, Thomas, et al. “Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study.JAMA Oncol, vol. 3, no. 9, Sept. 2017, p. e172411. Pubmed, doi:10.1001/jamaoncol.2017.2411.
Powles T, O’Donnell PH, Massard C, Arkenau H-T, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411.

Published In

JAMA Oncol

DOI

EISSN

2374-2445

Publication Date

September 14, 2017

Volume

3

Issue

9

Start / End Page

e172411

Location

United States

Related Subject Headings

  • Survival Rate
  • Retreatment
  • Response Evaluation Criteria in Solid Tumors
  • Neoplasm Staging
  • Middle Aged
  • Male
  • Liver Neoplasms
  • Humans
  • Follow-Up Studies
  • Female