Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies

  • Pedro C. Barata
  • Dhrmesh Gopalakrishnan
  • Vadim S. Koshkin
  • Prateek Mendiratta
  • Matt Karafa
  • Kimberly Allman
  • Allison Martin
  • Jennifer Beach
  • Pam Profusek
  • Allison Tyler
  • Laura Wood
  • Moshe Ornstein
  • Timothy Gilligan
  • Brian I. Rini
  • Jorge A. Garcia
  • Petros Grivas
Original Research Article

Abstract

Background

Little is known about the outcomes, safety, and response to subsequent therapies of patients with metastatic urothelial carcinoma (mUC) treated with atezolizumab outside clinical trials.

Objectives

The objectives of the study include to report the clinical efficacy and safety of atezolizumab, and the response to future therapies in clinical practice outside clinical trials.

Patient and Methods

This is a retrospective, single-center study including consecutive patients with confirmed mUC who received at least one dose of atezolizumab 1200 mg every 3 weeks between May 2016 and April 2017.

Results

Seventy-nine patients, median age 72 years (range 29–93), 71% men and 76% ECOG PS 0–1, were identified. Most patients (79%) had primary cancer in the bladder, 62% had prior surgery, and 75% received at least one prior line of treatment (34 patients had prior cisplatin-based chemotherapy). Best response included 18% partial response, 29% stable disease, and 53% progressive disease. Patients were on atezolizumab for a median of 2.7 months (95%CI, 1.8–3.6) and median PFS was 3.2 months (95%CI, 1.6–4.8). A total of 33 (42%) patients had significant (any cause) AEs, including grade 4 hyperbilirubinemia in two patients; no toxic deaths were reported. At time of data analysis, only 18% of patients received at least one subsequent line of treatment for a median of 1.8 months (95%CI, 0.0–5.0) while 42% were referred to palliative care/hospice or died.

Conclusions

Patients with mUC who progressed on atezolizumab were unlikely to receive subsequent systemic treatments and the benefit of those treatments appeared limited in our cohort. The findings may impact timing and designs of clinical trials in mUC.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

The authors declare no conflict of interest specifically relevant to this study. PG was one of the lead co-investigators on the IMvigor210 trial. Unrelated consulting is included in the comments. This retrospective study was approved by the Cleveland Clinic IRB (research protocol IRB#14–1222). Patient data was collected in compliance with guidelines and informed consent was waived for this study.

Supplementary material

11523_2018_561_MOESM1_ESM.pdf (117 kb)
ESM 1 (PDF 116 kb)

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Pedro C. Barata
    • 1
  • Dhrmesh Gopalakrishnan
    • 2
  • Vadim S. Koshkin
    • 1
  • Prateek Mendiratta
    • 1
  • Matt Karafa
    • 3
  • Kimberly Allman
    • 1
  • Allison Martin
    • 1
  • Jennifer Beach
    • 1
  • Pam Profusek
    • 1
  • Allison Tyler
    • 1
  • Laura Wood
    • 1
  • Moshe Ornstein
    • 1
  • Timothy Gilligan
    • 1
  • Brian I. Rini
    • 1
  • Jorge A. Garcia
    • 1
  • Petros Grivas
    • 1
    • 4
  1. 1.Department of Hematology & Medical OncologyTaussig Cancer Institute Cleveland ClinicClevelandUSA
  2. 2.Department of Hospital MedicineCleveland ClinicClevelandUSA
  3. 3.Quantitative Health SciencesCleveland ClinicClevelandUSA
  4. 4.Department of Medicine, Division of OncologyUniversity of Washington and Fred Hutchinson Cancer Research Center, Seattle Cancer Care AllianceSeattleUSA

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